Tahir A Rizvi

@article{Ahmad2026b,

title = {Dysregulated host miRNAs with antiviral potential against SARS-CoV-2 identified from COVID-19 patients},

author = {Waqar Ahmad and Bushra Gull and Jasmin Baby and Neena G. Panicker and Thanumol Abdul Khader and Tahir A. Rizvi and Farah Mustafa},

doi = {10.1186/s12967-026-08094-1},

issn = {1479-5876},

year  = {2026},

date = {2026-12-00},

urldate = {2026-12-00},

journal = {J Transl Med},

volume = {24},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {\textbf{Background}

MicroRNAs (miRNAs) are small RNA molecules implicated in controlling most cellular processes by either deadenylating/degrading mRNA transcripts or inhibiting their translation. Viruses and their hosts utilize miRNAs for regulating gene expression, targeting both cellular and viral mRNAs. Since the onset of the COVID-19 pandemic, numerous studies have aimed at elucidating the role of host responses at the molecular and cellular levels in determining disease severity among infected individuals. However, the precise interactions between SARS-CoV-2 and host miRNAs, and their biological impact on virus replication or pathogenesis remains poorly understood.

\textbf{Methods}

Employing miRNAseq and real time PCR, we have previously identified dysregulated host miRNAs in a large cohort of SARS-CoV-2 infected individuals. In this study, we used specialized bioinformatic and computational tools, as well as 3D docking analysis to investigate the ability of the dysregulated miRNAs observed in these COVID-19 patients to target the SARS-CoV-2 genome.

\textbf{Results}

Our analyses reveal that some of the differentially regulated, COVID-19-specific miRNAs had the potential to directly target the SARS-CoV-2 genome or its sub-genomic transcripts essential for virion formation, viral replication, and infection. These included mRNAs for non-structural and structural proteins, suggesting that SARS-CoV-2 may benefit from these miRNAs for its replication or immune evasion. Further miRNA target gene analysis revealed how these miRNAs may also target host cellular pathways, including FoxO, AMPK, mTOR, PI3-Akt, and ErbB, essential for critical cellular functions. Interestingly, these pathways are also disrupted during conditions like diabetes, aging, and neurodegenerative disorders, as well as frequently exploited by viruses to enhance virus replication and pathogenesis.

\textbf{Conclusions}

In summary, this work identifies several endogenous host miRNAs dysregulated during SARS-CoV-2 infection that can be exploited to not only target the virus itself, but also mitigate severe disease during future pandemic(s) with any SARS-CoV-2 variant-of-concern (VOC). Thus, it offers promising new potential molecular targets for therapeutic development, complementing existing antiviral strategies. Coupled with identification of cellular pathways involved in pathogenesis, these findings underscore the profound impact of miRNAs on viral pathogenesis, host metabolism, and immune responses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ahmad2026,

title = {Shaping Cell Identity: Global Transcriptome and Pathway Shifts during Mouse Mammary Epithelial Cell Differentiation},

author = {Waqar Ahmad and Neena Gopinathan Panicker and Tahir A. Rizvi and Farah Mustafa},

doi = {10.34133/csbj.0055},

issn = {2001-0370},

year  = {2026},

date = {2026-03-01},

urldate = {2026-03-01},

journal = {Comput Struct Biotechnol J},

volume = {35},

number = {1},

publisher = {American Association for the Advancement of Science (AAAS)},

abstract = {Mouse mammary epithelial cells possess a remarkable ability to regenerate the entire mammary gland through precisely regulated differentiation, involving complex molecular, morphological, and functional changes. Here, we performed comprehensive transcriptomic profiling of HC11 mouse mammary epithelial cells undergoing lactogenic differentiation using RNA sequencing and integrative bioinformatics. We identified 566 differentially expressed genes, reflecting extensive transcriptional reprogramming and activation of biosynthetic, metabolic, and secretory programs. Strong up-regulation of terminal and lactogenic differentiation markers, including Wap, Csn2, Lpl, Cd36, Lalba, Btn1a1, Xdh, Gata3, and Cebpb, signified maturation into a secretory phenotype. Functional evaluation via gene set enrichment analysis revealed transcriptional enrichment of mTOR, prolactin, insulin, ErbB, and autophagy-associated pathways, consistent with anabolic readiness and terminal differentiation. Conversely, p53, Wnt, and FoxO pathways were down-regulated, marking a transition from proliferation to differentiation. Transcription factors (FoxO1, Zbtb16, and Srebf1) and epigenetic regulators (Gadd45a and Hist1h1e) exhibited dynamic changes, underscoring coordinated transcriptional and chromatin remodeling. Gene set enrichment and protein–protein interaction analyses identified 10 hub genes, Agt, Ccnd1, Igf1, Mki67, Myc, Calm4, Rasgrp1, Cd69, Il6, and Pecam1, as central drivers of differentiation. Clustering of uniquely regulated genes further implicated roles in milk synthesis, protease activity, and lineage stabilization. Together, these findings define a transcriptional framework for lactogenic differentiation in the HC11 cell line model and provide a basis for future mechanistic studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jehad2025b,

title = {Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication},

author = {Mohammad Abdullah Jehad and Lizna M Ali and Vineeta N Pillai and Suresha G Prabhu and Farah Mustafa and Tahir A Rizvi},

editor = {Christian Münz},

doi = {10.1093/femsre/fuaf066},

issn = {1574-6976},

year  = {2026},

date = {2026-01-10},

urldate = {2026-01-10},

journal = {FEMS Microbiology Reviews},

volume = {50},

publisher = {Oxford University Press (OUP)},

abstract = {Retroviruses are exclusive group of positive-sense RNA viruses defined by their ability to reverse transcribe their RNA genome and integrate it into the host’s chromosomal DNA. This distinctive replication strategy enables persistent infection and has profoundly shaped our understanding of molecular biology, gene regulation, and evolution. Retroviruses have contributed to landmark discoveries, including the identification of oncogenes, mechanisms of transcriptional control, and the development of gene therapy vectors. This review provides an updated overview of retroviral molecular biology, emphasizing the coordinated steps of the viral life cycle and emerging insights that are reshaping classical models. It explores virion structure, genome organization, and the interplay of cis-acting sequences and trans-acting factors that govern replication. Special focus is given to recent advances in understanding nuclear trafficking of capsids, spatial dynamics of reverse transcription and integration leading to provirus formation, RNA nuclear export, and selective genome packaging. The structural and functional roles of viral proteins, particularly Gag, are discussed in the context of assembly and maturation. By integrating foundational concepts with new discoveries, this review highlights the molecular sophistication of retroviral replication and identifies outstanding questions that guide future research, with implications extending to antiviral strategies, gene therapy, cancer biology, and evolution.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mustafa2025,

title = {miRNA biomarkers for prognosis and therapy monitoring in a multi-ethnic cohort with SARS-CoV-2 infection},

author = {Farah Mustafa and Waqar Ahmad and Bushra Gull and Jasmin Baby and Neena G. Panicker and Thanumol Abdul Khader and Hala Abdul Baki and Erum Rehman and Asif M. Salim and Rubina L. G. Ahmed and Hamda H. Khansaheb and Maya Habous and Laila M. J. A. AlDabal and Soumeya Jaballah and Saif S. Alqassim and Alawi Alsheikh-Ali and Tahir A Rizvi},

doi = {10.1038/s41598-025-15248-6},

issn = {2045-2322},

year  = {2025},

date = {2025-12-00},

urldate = {2025-12-00},

journal = {Sci Rep},

volume = {15},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {This study aimed to identify miRNA-based biomarkers in a multi-ethnic cohort of SARS-CoV-2-infected individuals to enhance preparedness for future variants of concern. A total of 31 healthy controls and 154 infected patients were enrolled, from which 13 matched controls and 38 infected nasal swab samples were analyzed using miRNA sequencing, followed by qRT-PCR validation. Among the 1788 miRNAs detected, 14 differentially expressed miRNAs and four novel miRNAs were identified, with novel-miR-264-5p showing a ≥ 2-fold change. Correlation with clinical markers highlighted several miRNAs as potential prognostic biomarkers. Seven miRNAs, including miR-146b-3p, miR-154-5p, miR-5010-3p, miR-127-3p, miR-335-3p, miR-30c-5p, and miR-202-5p, showed strong prognostic potential. Combined ROC analysis demonstrated that a panel of top-performing miRNAs significantly enhanced diagnostic accuracy (AUC 0.939–0.972; p < 0.0001). Moreover, integrating miRNA biomarkers with clinical parameters further improved performance (AUC = 0.982; p < 0.0001). miR-146b-3p, detected exclusively in infected patients, emerged as a highly specific biomarker. Several nasal miRNAs mirrored blood profiles, highlighting the utility of nasal swabs for non-invasive monitoring. Collectively, these findings suggest that miRNA-based biomarkers, alone or combined with clinical markers, offer a promising platform for COVID-19 prognosis and diagnosis, and lay groundwork for future miRNA-based antiviral strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jaballah2025,

title = {Retroviral Vector Technology for Gene Therapy: History, Current Landscape, and Future Prospects},

author = {Soumeya Ali Jaballah and Lizna M Ali and Mohammad Abdullah Jehad and Shaima Akhlaq and Tahir A. Rizvi and Farah Mustafa},

doi = {10.1016/j.jmb.2025.169473},

issn = {0022-2836},

year  = {2025},

date = {2025-12-00},

urldate = {2025-12-00},

journal = {Journal of Molecular Biology},

volume = {437},

number = {24},

publisher = {Elsevier BV},

abstract = {The concept of gene therapy and its practice has been prevalent for over five decades. The first successful retroviral vector-based gene therapy trial took place ∼35 years ago, followed by several setbacks. However, recent years have seen a surge in successes, offering new hope to patients with genetic and other disorders once deemed untreatable. Over the past decade, rapid advancements in molecular biology have led to the development of safer and more effective gene therapy strategies with various gene delivery systems now in use. Among these, viral vectors such as retroviruses, adenoviruses, and adeno-associated viruses are the most widely employed in both research and clinical settings. This is due to their natural efficiency in delivering genetic material into target cells. Among these viral vectors, retroviruses stand out for their unique ability to reverse-transcribe and integrate their genetic material into the host genome, ensuring stable and long-term gene expression. This review highlights advances in retroviral vector development, examining both their therapeutic potential and associated challenges. It also explores strategies for vector production, including transient and stable systems tailored to meet clinical and regulatory demands. Significant progress is discussed in mitigating insertional mutagenesis and vector silencing. As a result, next-generation retroviral vectors with improved safety and efficacy have made it past regulatory approval and are commercially available. Current innovations include replication-competent, non-integrating, integration-retargeted, and hybrid CRISPR/Cas-expressing retroviral vectors undergoing pre-clinical and clinical investigations. This reflects a new era in gene therapy, with retroviral vectors reimagined for greater precision, control, and therapeutic impact.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Khader2024,

title = {Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax},

author = {Thanumol Abdul Khader and Waqar Ahmad and Shaima Akhlaq and Neena Gopinathan Panicker and Bushra Gull and Jasmin Baby and Tahir A. Rizvi and Farah Mustafa},

doi = {10.1038/s42003-024-07139-9},

issn = {2399-3642},

year  = {2024},

date = {2024-12-00},

urldate = {2024-12-00},

journal = {Commun Biol},

volume = {7},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {The mouse mammary tumor virus (MMTV) encodes a 5’ element crucial for transcription of its genome along with the Rem/Rem-responsive element (RmRE) responsible for nuclear export of this unspliced RNA. Whether the 5’ element is Rem-responsive or has any functional interaction with host/viral factors to facilitate MMTV gene expression was tested in this study. Our results reveal that the 5’ element is non-responsive to Rem, but can be transactivated by both HIV Tat and HTLV-1 Tax activators. Reciprocally, MMTV could transactivate not only HIV TAR (similar to HTLV Tax), but also its 5’ element. Furthermore, we reveal involvement of pTEFb, a general elongation factor associated with transactivation by Tat/Tax. This makes MMTV the first betaretrovirus to encode both Rem/RRE and Tat/TAR-Tax/TRE-like transcription regulatory systems. This study should enhance not only our understanding of retrovirus replication and virally-induced cancers/immunodeficiency syndromes, but also development of improved retroviral vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gull2024,

title = {Identification and characterization of host miRNAs that target the mouse mammary tumour virus (MMTV) genome},

author = {Bushra Gull and Waqar Ahmad and Jasmin Baby and Neena G. Panicker and Thanumol Abdul Khader and Tahir A. Rizvi and Farah Mustafa},

doi = {10.1098/rsob.240203},

issn = {2046-2441},

year  = {2024},

date = {2024-12-00},

urldate = {2024-12-00},

journal = {Open Biol.},

volume = {14},

number = {12},

publisher = {The Royal Society},

abstract = {The intricate interplay between viruses and hosts involves microRNAs (miRNAs) to regulate gene expression by targeting cellular/viral messenger RNAs (mRNAs). Mouse mammary tumour virus (MMTV), the aetiological agent of breast cancer and leukaemia/lymphomas in mice, provides an ideal model to explore how viral and host miRNAs interact to modulate virus replication and tumorigenesis. We previously reported dysregulation of host miRNAs in MMTV-infected mammary glands and MMTV-induced tumours, suggesting a direct interaction between MMTV and miRNAs. To explore this further, we systematically examined all potential interactions between host miRNAs and the MMTV genome using advanced prediction tools. Leveraging miRNA sequencing data from MMTV-expressing cells, we identified dysregulated miRNAs capable of targeting MMTV. Docking analysis validated the interaction of three dysregulated miRNAs with the MMTV genome, followed by confirmation with RNA immunoprecipitation assays. We further identified host targets of these miRNAs using mRNA sequencing data from MMTV-expressing cells. These findings should enhance our understanding of how MMTV replicates and interacts with the host to induce cancer in mice, a model important for cancer research. Given MMTV’s potential zoonosis and association with human breast cancer/lymphomas, if confirmed, our work could further lead to novel miRNA-based antivirals/therapeutics to prevent possible MMTV transmission and associated cancers in humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{BABY2024168738,

title = {The Host miR-17-92 Cluster Negatively Regulates Mouse Mammary Tumor Virus (MMTV) Replication Primarily Via Cluster Member miR-92a},

author = {Jasmin Baby and Bushra Gull and Waqar Ahmad and Hala Abdul Baki and Thanumol Abdul Khader and Neena G. Panicker and Shaima Akhlaq and T. A. Rizvi and Farah Mustafa},

url = {https://www.sciencedirect.com/science/article/pii/S0022283624003474},

doi = {https://doi.org/10.1016/j.jmb.2024.168738},

issn = {0022-2836},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Journal of Molecular Biology},

volume = {436},

number = {20},

pages = {168738},

abstract = {The mouse mammary tumor virus (MMTV) is a well-known causative agent of breast cancer in mice. Previously, we have shown that MMTV dysregulates expression of the host miR-17-92 cluster in MMTV-infected mammary glands and MMTV-induced tumors. This cluster, better known as oncomiR-1, is frequently dysregulated in cancers, particularly breast cancer. In this study, our aim was to uncover a functional interaction between MMTV and the cluster. Our results reveal that MMTV expression led to dysregulation of the cluster in both mammary epithelial HC11 and HEK293T cells with the expression of miR-92a cluster member being affected the most. Conversely, overexpression of the whole or partial cluster significantly repressed MMTV expression. Notably, overexpression of cluster member miR-92a alone repressed MMTV expression to the same extent as overexpression of the complete/partial cluster. Inhibition of miR-92a led to nearly a complete restoration of MMTV expression, while deletion/substitution of the miR-92a seed sequence rescued MMTV expression. Dual luciferase assays identified MMTV genomic RNA as the potential target of miR-92a. These results show that the miR-17-92 cluster acts as part of the cell’s well-known miRNA-based anti-viral response to thwart incoming MMTV infection. Thus, this study provides the first evidence highlighting the biological significance of host miRNAs in regulating MMTV replication and potentially influencing tumorigenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1371/journal.pbio.3002827,

title = {MMTV RNA packaging requires an extended long-range interaction for productive Gag binding to packaging signals},

author = {Suresha G. Prabhu and Vineeta N. Pillai and Lizna Mohamed Ali and Valérie Vivet-Boudou and Akhil Chameettachal and Serena Bernacchi and Farah Mustafa and Roland Marquet and T. A. Rizvi},

url = {https://doi.org/10.1371/journal.pbio.3002827},

doi = {10.1371/journal.pbio.3002827},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {PLOS Biology},

volume = {22},

number = {10},

pages = {1-34},

publisher = {Public Library of Science},

abstract = {The packaging of genomic RNA (gRNA) into retroviral particles relies on the specific recognition by the Gag precursor of packaging signals (Psi), which maintain a complex secondary structure through long-range interactions (LRIs). However, it remains unclear whether the binding of Gag to Psi alone is enough to promote RNA packaging and what role LRIs play in this process. Using mouse mammary tumor virus (MMTV), we investigated the effects of mutations in 4 proposed LRIs on gRNA structure and function. Our findings revealed the presence of an unsuspected extended LRI, and hSHAPE revealed that maintaining a wild-type–like Psi structure is crucial for efficient packaging. Surprisingly, filter-binding assays demonstrated that most mutants, regardless of their packaging capability, exhibited significant binding to Pr77Gag, suggesting that Gag binding to Psi is insufficient for efficient packaging. Footprinting experiments indicated that efficient RNA packaging is promoted when Pr77Gag binds to 2 specific sites within Psi, whereas binding elsewhere in Psi does not lead to efficient packaging. Taken together, our results suggest that the 3D structure of the Psi/Pr77Gag complex regulates the assembly of viral particles around gRNA, enabling effective discrimination against other viral and cellular RNAs that may also bind Gag efficiently.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Krishnan2023,

title = {Identification of a putative Gag binding site critical for feline immunodeficiency virus genomic RNA packaging},

author = {A. Krishnan and L. M. Ali and Suresha G Prabhu and V. N. Pillai and A. Chameettachal and Valérie Vivet-Boudou and Serena Bernacchi and F. Mustafa and Roland Marquet and T. A. Rizvi},

doi = {10.1261/rna.079840.123},

issn = {1469-9001},

year  = {2024},

date = {2024-01-00},

urldate = {2024-01-00},

journal = {RNA},

volume = {30},

number = {1},

pages = {68--88},

publisher = {Cold Spring Harbor Laboratory},

abstract = {The retroviral Gag precursor plays a central role in the selection and packaging of viral genomic RNA (gRNA) by binding to virus-specific packaging signal(s) (psi or ψ). Previously, we mapped the feline immunodeficiency virus (FIV) ψ to two discontinuous regions within the 5′ end of the gRNA that assumes a higher order structure harboring several structural motifs. To better define the region and structural elements important for gRNA packaging, we methodically investigated these FIV ψ sequences using genetic, biochemical, and structure–function relationship approaches. Our mutational analysis revealed that the unpaired U85CUG88 stretch within FIV ψ is crucial for gRNA encapsidation into nascent virions. High-throughput selective 2′ hydroxyl acylation analyzed by primer extension (hSHAPE) performed on wild type (WT) and mutant FIV ψ sequences, with substitutions in the U85CUG88 stretch, revealed that these mutations had limited structural impact and maintained nucleotides 80–92 unpaired, as in the WT structure. Since these mutations dramatically affected packaging, our data suggest that the single-stranded U85CUG88 sequence is important during FIV RNA packaging. Filter-binding assays performed using purified FIV Pr50Gag on WT and mutant U85CUG88 ψ RNAs led to reduced levels of Pr50Gag binding to mutant U85CUG88 ψ RNAs, indicating that the U85CUG88 stretch is crucial for ψ RNA–Pr50Gag interactions. Delineating sequences important for FIV gRNA encapsidation should enhance our understanding of both gRNA packaging and virion assembly, making them potential targets for novel retroviral therapeutic interventions, as well as the development of FIV-based vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tay2023,

title = {HLA class I associations with the severity of COVID-19 disease in the United Arab Emirates},

author = {Guan K. Tay and Halima Alnaqbi and Sarah Chehadeh and Braulio Peramo and Farah Mustafa and Tahir A. Rizvi and Bassam H. Mahboub and Maimunah Uddin and Nawal Alkaabi and Eman Alefishat and Herbert F. Jelinek and Habiba Alsafar and },

editor = {Engin Berber},

doi = {10.1371/journal.pone.0285712},

issn = {1932-6203},

year  = {2023},

date = {2023-09-14},

journal = {PLoS ONE},

volume = {18},

number = {9},

publisher = {Public Library of Science (PLoS)},

abstract = {SARS-CoV-2 appears to induce diverse innate and adaptive immune responses, resulting in different clinical manifestations of COVID-19. Due to their function in presenting viral peptides and initiating the adaptive immune response, certain Human Leucocyte Antigen (HLA) alleles may influence the susceptibility to severe SARS-CoV-2 infection. In this study, 92 COVID-19 patients from 15 different nationalities, with mild (n = 30), moderate (n = 35), and severe (n = 27) SARS-CoV-2 infection, living in the United Arab Emirates (UAE) were genotyped for the Class I HLA -A, -C, and -B alleles using next-generation sequencing (NGS) between the period of May 2020 to June 2020. Alleles and inferred haplotype frequencies in the hospitalized patient group (those with moderate to severe disease, n = 62) were compared to non-hospitalized patients (mild or asymptomatic, n = 30). An interesting trend was noted between the severity of COVID-19 and the HLA-C*04 (P = 0.0077) as well as HLA-B*35 (P = 0.0051) alleles. The class I haplotype HLA-C*04-B*35 was also significantly associated (P = 0.0049). The involvement of inflammation, HLA-C*04, and HLA-B*35 in COVID-19 severity highlights the potential roles of both the adaptive and innate immune responses against SARS-CoV-2. Both alleles have been linked to several respiratory diseases, including pulmonary arterial hypertension along with infections caused by the coronavirus and influenza. This study, therefore, supports the potential use of HLA testing in prioritizing public healthcare interventions for patients at risk of COVID-19 infection and disease progression, in addition to providing personalized immunotherapeutic targets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37145095,

title = {Differentially-regulated miRNAs in COVID-19: A systematic review},

author = {Waqar Ahmad and Bushra Gull and Jasmin Baby and Neena G Panicker and Thanumol A Khader and Shaima Akhlaq and T. A. Rizvi and F. Mustafa},

doi = {10.1002/rmv.2449},

issn = {1099-1654},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Rev Med Virol},

volume = {33},

number = {4},

pages = {e2449},

abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease of 2019 (COVID-19) that infected more than 760 million people worldwide with over 6.8 million deaths to date. COVID-19 is one of the most challenging diseases of our times due to the nature of its spread, its effect on multiple organs, and an inability to predict disease prognosis, ranging from being completely asymptomatic to death. Upon infection, SARS-CoV-2 alters the host immune response by changing host-transcriptional machinery. MicroRNAs (miRNAs) are regarded as post-transcriptional regulators of gene expression that can be perturbed by invading viruses. Several in vitro and in vivo studies have reported such dysregulation of host miRNA expression upon SARS-CoV-2 infection. Some of this could occur as an anti-viral response of the host to the viral infection. Viruses themselves can counteract that response by mounting their own pro-viral response that facilitates virus infection, an aspect which may cause pathogenesis. Thus, miRNAs could serve as possible disease biomarkers in infected people. In the current review, we have summarised and analysed the existing data about miRNA dysregulation in patients infected with SARS-CoV-2 to determine their concordance between studies, and identified those that could serve as potential biomarkers during infection, disease progression, and death, even in people with other co-morbidities. Having such biomarkers can be vital in not only predicting COVID-19 prognosis, but also the development of novel miRNA-based anti-virals and therapeutics which can become invaluable in case of the emergence of new viral variants with pandemic potential in the future.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37243196,

title = {Global Down-regulation of Gene Expression Induced by Mouse Mammary Tumor Virus (MMTV) in Normal Mammary Epithelial Cells},

author = {Waqar Ahmad and Neena G Panicker and Shaima Akhlaq and Bushra Gull and Jasmin Baby and Thanumol A Khader and T. A. Rizvi and F. Mustafa},

doi = {10.3390/v15051110},

issn = {1999-4915},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Viruses},

volume = {15},

number = {5},

abstract = {Mouse mammary tumor virus (MMTV) is a  that causes breast cancer in mice. The mouse mammary epithelial cells are the most permissive cells for MMTV, expressing the highest levels of virus upon infection and being the ones later transformed by the virus due to repeated rounds of infection/superinfection and integration, leading eventually to mammary tumors. The aim of this study was to identify genes and molecular pathways dysregulated by MMTV expression in mammary epithelial cells. Towards this end, mRNAseq was performed on normal mouse mammary epithelial cells stably expressing MMTV, and expression of host genes was analyzed compared with cells in its absence. The identified differentially expressed genes (DEGs) were grouped on the basis of gene ontology and relevant molecular pathways. Bioinformatics analysis identified 12 hub genes, of which 4 were up-regulated (Angp2, Ccl2, Icam, and Myc) and 8 were down-regulated (Acta2, Cd34, Col1a1, Col1a2, Cxcl12, Eln, Igf1, and Itgam) upon MMTV expression. Further screening of these DEGs showed their involvement in many diseases, especially in breast cancer progression when compared with available data. Gene Set Enrichment Analysis (GSEA) identified 31 molecular pathways dysregulated upon MMTV expression, amongst which the PI3-AKT-mTOR was observed to be the central pathway down-regulated by MMTV. Many of the DEGs and 6 of the 12 hub genes identified in this study showed expression profile similar to that observed in the PyMT mouse model of breast cancer, especially during tumor progression. Interestingly, a global down-regulation of gene expression was observed, where nearly 74% of the DEGs in HC11 cells were repressed by MMTV expression, an observation similar to what was observed in the PyMT mouse model during tumor progression, from hyperplasia to adenoma to early and late carcinomas. Comparison of our results with the Wnt1 mouse model revealed further insights into how MMTV expression could lead to activation of the Wnt1 pathway independent of insertional mutagenesis. Thus, the key pathways, DEGs, and hub genes identified in this study can provide important clues to elucidate the molecular mechanisms involved in MMTV replication, escape from cellular anti-viral response, and potential to cause cell transformation. These data also validate the use of the MMTV-infected HC11 cells as an important model to study early transcriptional changes that could lead to mammary cell transformation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN25,

title = {Understanding Retroviral Life Cycle and its Genomic RNA Packaging},

author = {A. Chameettachal and F. Mustafa and T. A. Rizvi},

doi = {10.1016/j.jmb.2022.167924},

issn = {0022-2836},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {J Mol Biol},

volume = {435},

number = {3},

pages = {167924},

abstract = {Members of the family Retroviridae are important animal and human pathogens. Being obligate parasites, their replication involves a series of steps during which the virus hijacks the cellular machinery. Additionally, many of the steps of retrovirus replication are unique among viruses, including reverse transcription, integration, and specific packaging of their genomic RNA (gRNA) as a dimer. Progress in retrovirology has helped identify several molecular mechanisms involved in each of these steps, but many are still unknown or remain controversial. This review summarizes our present understanding of the molecular mechanisms involved in various stages of retrovirus replication. Furthermore, it provides a comprehensive analysis of our current understanding of how different retroviruses package their gRNA into the assembling virions. RNA packaging in retroviruses holds a special interest because of the uniqueness of packaging a dimeric genome. Dimerization and packaging are highly regulated and interlinked events, critical for the virus to decide whether its unspliced RNA will be packaged as a "genome" or translated into proteins. Finally, some of the outstanding areas of exploration in the field of RNA packaging are highlighted, such as the role of epitranscriptomics, heterogeneity of transcript start sites, and the necessity of functional polyA sequences. An in-depth knowledge of mechanisms that interplay between viral and cellular factors during virus replication is critical in understanding not only the virus life cycle, but also its pathogenesis, and development of new antiretroviral compounds, vaccines, as well as retroviral-based vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN115,

title = {Expression, purification, and functional characterization of soluble recombinant full-length simian immunodeficiency virus (SIV) Pr55(Gag)},

author = {V. N. Pillai and L. M. Ali and S. G. Prabhu and A. Krishnan and S. Tariq and F. Mustafa and T. A. Rizvi},

doi = {10.1016/j.heliyon.2023.e12892},

issn = {2405-8440 (Print) 2405-8440},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Heliyon},

volume = {9},

number = {1},

pages = {e12892},

abstract = {The simian immunodeficiency virus (SIV) precursor polypeptide Pr55(Gag) drives viral assembly and facilitates specific recognition and packaging of the SIV genomic RNA (gRNA) into viral particles. While several studies have tried to elucidate the role of SIV Pr55(Gag) by expressing its different components independently, studies using full-length SIV Pr55(Gag) have not been conducted, primarily due to the unavailability of purified and biologically active full-length SIV Pr55(Gag). We successfully expressed soluble, full-length SIV Pr55(Gag) with His(6)-tag in bacteria and purified it using affinity and gel filtration chromatography. In the process, we identified within Gag, a second in-frame start codon downstream of a putative Shine-Dalgarno-like sequence resulting in an additional truncated form of Gag. Synonymously mutating this sequence allowed expression of full-length Gag in its native form. The purified Gag assembled into virus-like particles (VLPs) in vitro in the presence of nucleic acids, revealing its biological functionality. In vivo experiments also confirmed formation of functional VLPs, and quantitative reverse transcriptase PCR demonstrated efficient packaging of SIV gRNA by these VLPs. The methodology we employed ensured the availability of >95% pure, biologically active, full-length SIV Pr55(Gag) which should facilitate future studies to understand protein structure and RNA-protein interactions involved during SIV gRNA packaging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN23,

title = {Detection of SARS-CoV-2 in COVID-19 Patient Nasal Swab Samples Using Signal Processing},

author = {M. A. Ahmad and L. J. A. Olule and M. Meetani and F. A. Sheikh and R. A. Blooshi and N. G. Panicker and F. Mustafa and T. A. Rizvi},

doi = {10.1109/jstsp.2021.3134073},

issn = {1932-4553 (Print) 1932-4553},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {IEEE J Sel Top Signal Process},

volume = {16},

number = {2},

pages = {164-174},

abstract = {This work presents an opto-electrical method that measures the viral nucleocapsid protein and anti-N antibody interactions to differentiate between SARS-CoV-2 negative and positive nasal swab samples. Upon light exposure of the patient nasal swab sample mixed with the anti-N antibody, charge transfer (CT) transitions within the altered protein folds are initiated between the charged amino acids side chain moieties and the peptide backbone that play the role of donor and acceptor groups. A Figure of Merit (FOM) was introduced to correlate the relative variations of the samples with and without antibody at two different voltages. Empirically, SARS-CoV-2 in patient nasal swab samples was detected within two minutes, if an extracted FOM threshold of >1 was achieved; otherwise, the sample wasconsidered negative.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN37,

title = {Comparative Experimental Investigation of Biodegradable Antimicrobial Polymer-Based Composite Produced by 3D Printing Technology Enriched with Metallic Particles},

author = {W. Ahmed and A. H. Al-Marzouqi and M. H. Nazir and T. A. Rizvi and E. Zaneldin and M. Khan},

doi = {10.3390/ijms231911235},

issn = {1422-0067},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Int J Mol Sci},

volume = {23},

number = {19},

abstract = {Due to the prevailing existence of the COVID-19 pandemic, novel and practical strategies to combat pathogens are on the rise worldwide. It is estimated that, globally, around 10% of hospital patients will acquire at least one healthcare-associated infection. One of the novel strategies that has been developed is incorporating metallic particles into polymeric materials that neutralize infectious agents. Considering the broad-spectrum antimicrobial potency of some materials, the incorporation of metallic particles into the intended hybrid composite material could inherently add significant value to the final product. Therefore, this research aimed to investigate an antimicrobial polymeric PLA-based composite material enhanced with different microparticles (copper, aluminum, stainless steel, and bronze) for the antimicrobial properties of the hybrid composite. The prepared composite material samples produced with fused filament fabrication (FFF) 3D printing technology were tested for different time intervals to establish their antimicrobial activities. The results presented here depict that the sample prepared with 90% copper and 10% PLA showed the best antibacterial activity (99.5%) after just 20 min against different types of bacteria as compared to the other samples. The metallic-enriched PLA-based antibacterial sheets were remarkably effective against Staphylococcus aureus and Escherichia coli; therefore, they can be a good candidate for future biomedical, food packaging, tissue engineering, prosthetic material, textile industry, and other science and technology applications. Thus, antimicrobial sheets made from PLA mixed with metallic particles offer sustainable solutions for a wide range of applications where touching surfaces is a big concern.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN63,

title = {Impact of the Sinopharm's BBIBP-CorV vaccine in preventing hospital admissions and death in infected vaccinees: Results from a retrospective study in the emirate of Abu Dhabi, United Arab Emirates (UAE)},

author = {F. Ismail AlHosani and A. Eduardo Stanciole and B. Aden and A. Timoshkin and O. Najim and W. Abbas Zaher and F. AlSayedsaleh AlDhaheri and S. Al Mazrouie and T. A. Rizvi and F. Mustafa},

doi = {10.1016/j.vaccine.2022.02.039},

issn = {0264-410X (Print) 0264-410x},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Vaccine},

volume = {40},

number = {13},

pages = {2003-2010},

abstract = {BACKGROUND: This is a community-based, retrospective, observational study conducted to determine effectiveness of the BBIBP-CorV inactivated vaccine in the real-world setting against hospital admissions and death. STUDY DESIGN: Study participants were selected from 214,940 PCR-positive cases of COVID-19 reported to the Department of Health, Abu Dhabi Emirate, United Arab Emirates (UAE) between September 01, 2020 and May 1, 2021. Of these, 176,640 individuals were included in the study who were aged ≥ 15 years with confirmed COVID-19 positive status who had records linked to their vaccination status. Those with incomplete or missing records were excluded (n = 38,300). Study participants were divided into three groups depending upon their vaccination status: fully vaccinated (two doses), partially vaccinated (single dose), and non-vaccinated. Study outcomes included COVID-19-related admissions to hospital general and critical care wards and death. Vaccine effectiveness for each outcome was based on the incidence density per 1000 person-years. RESULTS: The fully-, partially- and non-vaccinated groups included 62,931, 21,768 and 91,941 individuals, respectively. Based on the incidence rate ratios, the vaccine effectiveness in fully vaccinated individuals was 80%, 92%, and 97% in preventing COVID-19-related hospital admissions, critical care admissions, and death, respectively, when compared to the non-vaccinated group. No protection was observed for critical and non-critical care hospital admissions for the partially vaccinated group, while some protection against death was apparent, although statistically insignificant. CONCLUSIONS: In a COVID-19 pandemic, use of the Sinopharm BBIBP-CorV inactivated vaccine is effective in preventing severe disease and death in a two-dose regimen. Lack of protection with the single dose may be explained by insufficient seroconversion and/or neutralizing antibody responses, behavioral factors (i.e., false sense of protection), and/or other biological factors (emergence of variants, possibility of reinfection, duration of vaccine protection, etc.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN17,

title = {Early Years of Carbapenem-Resistant Enterobacterales Epidemic in Abu Dhabi},

author = {T. Pál and A. B. Butt and A. Ghazawi and J. Thomsen and T. A. Rizvi and Á Sonnevend},

doi = {10.3390/antibiotics11101435},

issn = {2079-6382 (Print) 2079-6382},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Antibiotics (Basel)},

volume = {11},

number = {10},

abstract = {Recent studies showed that the current endemic of carbapenem-resistant Enterobacterales (CRE) in the Emirate of Abu Dhabi is dominated by highly resistant Klebsiella pneumoniae clones ST14, ST231, and CC147, respectively. In the absence of continuous, molecular typing-based surveillance, it remained unknown whether they lately emerged and rapidly became dominant, or they had been present from the early years of the endemic. Therefore, antibiotic resistance, the presence of carbapenemase and 16S methylase genes, and the sequence types of CRE strains collected between 2009 and 2015 were compared with those collected between 2018 and 2019. It was found that members of these three clones, particularly those of the most prevalent ST14, started dominating already in the very early years of the CRE outbreak. Furthermore, while severely impacting the overall antibiotic resistance patterns, the effect of these clones was not exclusive: for example, increasing trends of colistin or decreasing rates of tigecycline resistance were also observed among nonclonal isolates. The gradually increasing prevalence of few major, currently dominating clones raises the possibility that timely, systematic, molecular typing-based surveillance could have provided tools to public health authorities for an early interference with the escalation of the local CRE epidemic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN30,

title = {The first nationwide surveillance of carbapenem-resistant Enterobacterales in the United Arab Emirates - increased association of Klebsiella pneumoniae CC14 clone with Emirati patients},

author = {Á Sonnevend and N. Abdulrazzaq and A. Ghazawi and J. Thomsen and G. Bharathan and L. Makszin and T. A. Rizvi and T. Pál},

doi = {10.1016/j.ijid.2022.04.034},

issn = {1201-9712},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Int J Infect Dis},

volume = {120},

pages = {103-112},

abstract = {OBJECTIVES: To assess the current prevalence, distribution, and main clonal types of carbapenem-resistant Enterobacterales (CRE) in the United Arab Emirates. METHODS: A total of 504 CRE collected over a 9-month period in 15 hospitals were studied. Antibiotic susceptibility and the presence of common carbapenemase, 16S methylase, and mobile colistin resistance genes were assessed. Selected strains forming larger clusters by pulsed field gel electrophoresis were subjected to whole genome sequencing to identify their sequence types and core genome MLST. RESULTS: Strains expressing OXA and NDM type carbapenemases and 16S methylases were present in all major hospitals. Considerable interhospital differences were noticed, suggesting the role of specific clones. A total of three major Klebsiella pneumoniae clones (CC14, ST231, and CC147) were identified, accounting for 48.6% of all CRE. All clones were significantly more resistant than sporadic isolates. CC14 strains exhibited a significant association with Emirati patients. CONCLUSIONS: Nearly half of CRE infections in the country are due to a limited number of clones. The data indicate the possibility of interhospital transmission, combined in some hospitals with inadequate stewardship practices. The study also revealed an association of the largest, most resistant clone (CC14) with Emirati patients. The specific reasons for it should be clarified by further investigations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN31,

title = {Molecular Characterization of MCR-1 Producing Enterobacterales Isolated in Poultry Farms in the United Arab Emirates},

author = {Á Sonnevend and W. Q. Alali and S. A. Mahmoud and A. Ghazawi and G. Bharathan and S. Melegh and T. A. Rizvi and T. Pál},

doi = {10.3390/antibiotics11030305},

issn = {2079-6382 (Print) 2079-6382},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Antibiotics (Basel)},

volume = {11},

number = {3},

abstract = {Data on the prevalence of MCR-producing Enterobacterales of animal origin are scarce from the Arabian Peninsula. We investigated the presence and variety of such strains from fecal specimens of poultry collected in four farms in the United Arab Emirates. Colonies from ten composite samples per farm grown on colistin-supplemented plates were PCR-screened for alleles of the mcr gene. Thirty-nine isolates selected based on species, colony morphology, and plasmid profile were subjected to whole genome sequencing. The panel of their resistance and virulence genes, MLST and cgMLST were established. Transferability and incompatibility types of the MCR-plasmids were determined. mcr-1.1 positive strains were identified in 36 of the 40 samples. Thirty-four multi-drug resistant Escherichia coli of 16 different sequence types, two Escherichia albertii, two Klebsiella pneumoniae and one Salmonella minnesota were identified. Beyond various aminoglycoside, tetracycline, and co-trimoxazole resistance genes, seven of them also carried ESBL genes and one bla(CMY-2). Six IncHI2, 26 IncI2 and 4 IncX4 MCR-plasmids were mobilized, in case of the IncHI2 plasmids co-transferring ampicillin, chloramphenicol and tetracycline resistance. The diversity of mcr-1 positive strains suggest a complex local epidemiology calling for a coordinated surveillance including animals, retail meat and clinical cases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hamouda2021,

title = {Wastewater surveillance for SARS-CoV-2: Lessons learnt from recent studies to define future applications},

author = {Mohamed Hamouda and Farah Mustafa and Munjed Maraqa and Tahir A Rizvi and Ashraf Aly Hassan},

doi = {10.1016/j.scitotenv.2020.143493},

issn = {0048-9697},

year  = {2021},

date = {2021-03-00},

urldate = {2021-03-00},

journal = {Science of The Total Environment},

volume = {759},

publisher = {Elsevier BV},

abstract = {Wastewater-based epidemiology (WBE) is successful in the detection of the spread of SARS-CoV-2. This review examines the methods used and results of recent studies on the quantification of SARS-CoV-2 in wastewater. WBE becomes essential, especially with virus transmission path uncertainty, limitations on the number of clinical tests that could be conducted, and a relatively long period for infected people to show symptoms. Wastewater surveillance was used to show the effect of lockdown on the virus spread. A WBE framework tailored for SARS-CoV-2 that incorporates lessons learnt from the reviewed studies was developed. Results of the review helped outline challenges facing the detection of SARS-CoV-2 in wastewater samples. A comparison between the various studies with regards to sample concentration and virus quantification was conducted. Five different primers sets were used for qPCR quantification; however, due to limited data availability, there is no consensus on the most sensitive primer. Correlating the slope of the relationship between the number of gene copies vs. the cumulative number of infections normalized to the total population served with the average new cases, suggests that qPCR results could help estimating the number of new infections. The correlation is improved when a lag period was introduced to account for asymptomatic infections. Based on lessons learnt from recent studies, it is recommended that future applications should consider the following: 1) ensuring occupational safety in managing sewage collection and processing, 2) evaluating the effectiveness of greywater disinfection, 3) measuring viral RNA decay due to biological and chemical activities during collection and treatment, 4) assessing the effectiveness of digital PCR, and 5) conducting large scale international studies that follow standardized protocols.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN14,

title = {Optical Detection of SARS-CoV-2 Utilizing Antigen-Antibody Binding Interactions},

author = {M. A. Ahmad and F. Mustafa and N. Panicker and T. A. Rizvi},

doi = {10.3390/s21196596},

issn = {1424-8220},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Sensors (Basel)},

volume = {21},

number = {19},

abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease (COVID-19) pandemic, is sweeping the world today. This study investigates the optical detection of SARS-CoV-2, utilizing the antigen-antibody binding interactions utilizing a light source from a smart phone and a portable spectrophotometer. The proof-of-concept is shown by detecting soluble preparations of spike protein subunits from SARS-CoV-2, followed by detection of the actual binding potential of the SARS-CoV-2 proteins with their corresponding antigens. The measured binding interactions for RBD and NCP proteins with their corresponding antibodies under different conditions have been measured and analyzed. Based on these observations, a "hump or spike" in light intensity is observed when a specific molecular interaction takes place between two proteins. The optical responses could further be analyzed using the principle component analysis technique to enhance and allows precise detection of the specific target in a multi-protein mixture.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN40,

title = {A purine loop and the primer binding site are critical for the selective encapsidation of mouse mammary tumor virus genomic RNA by Pr77Gag},

author = {A. Chameettachal and V. Vivet-Boudou and F. N. N. Pitchai and V. N. Pillai and L. M. Ali and A. Krishnan and S. Bernacchi and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1093/nar/gkab223},

issn = {0305-1048 (Print) 0305-1048},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Nucleic Acids Res},

volume = {49},

number = {8},

pages = {4668-4688},

abstract = {Retroviral RNA genome (gRNA) harbors cis-acting sequences that facilitate its specific packaging from a pool of other viral and cellular RNAs by binding with high-affinity to the viral Gag protein during virus assembly. However, the molecular intricacies involved during selective gRNA packaging are poorly understood. Binding and footprinting assays on mouse mammary tumor virus (MMTV) gRNA with purified Pr77Gag along with in cell gRNA packaging study identified two Pr77Gag binding sites constituting critical, non-redundant packaging signals. These included: a purine loop in a bifurcated stem-loop containing the gRNA dimerization initiation site, and the primer binding site (PBS). Despite these sites being present on both unspliced and spliced RNAs, Pr77Gag specifically bound to unspliced RNA, since only that could adopt the native bifurcated stem-loop structure containing looped purines. These results map minimum structural elements required to initiate MMTV gRNA packaging, distinguishing features that are conserved amongst divergent retroviruses from those perhaps unique to MMTV. Unlike purine-rich motifs frequently associated with packaging signals, direct involvement of PBS in gRNA packaging has not been documented in retroviruses. These results enhance our understanding of retroviral gRNA packaging/assembly, making it not only a target for novel therapeutic interventions, but also development of safer gene therapy vectors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN92,

title = {Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula},

author = {S. F. Mouftah and T. Pál and P. G. Higgins and A. Ghazawi and Y. Idaghdour and M. Alqahtani and A. S. Omrani and T. A. Rizvi and Á Sonnevend},

doi = {10.1007/s10096-021-04384-2},

issn = {0934-9723},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Eur J Clin Microbiol Infect Dis},

abstract = {To understand the reasons of successful spread of carbapenem-resistant Klebsiella pneumoniae ST14 (CRKP-ST14) in countries of the Arabian Peninsula, the resistome, capsular locus, carbapenemase carrying plasmid types, and core genome of isolates from the region were compared to global isolates. Thirty-nine CRKP-ST14 strains isolated from 13 hospitals in the United Arab Emirates, Bahrain, and Saudi Arabia were selected for whole genome sequencing on Illumina MiSeq platform based on the variety of carbapenemase genes carried and plasmids bearing these genes. Their resistome, capsular locus, and core genome MLST were compared to 173 CRKP-ST14 genomes available in public databases. The selected 39 CRKP-ST14 produced either NDM-1, OXA-48, OXA-162, OXA-232, KPC-2, or co-produced NDM-1 and an OXA-48-like carbapenemase. cgMLST revealed three clusters: 16 isolates from five UAE cities (C1), 11 isolates from three UAE cities and Bahrain (C2), and 5 isolates from Saudi Arabia (C3), respectively, and seven singletons. Resistance gene profile, carbapenemase genes, and their plasmid types were variable in both C1 and C2 clusters. The majority of CRKP-ST14 had KL2, but members of the C2 cluster and two further singletons possessed KL64 capsular locus. Based on cgMLST comparison of regional and global isolates, CRKP-ST14 with KL64 from four continents formed a distinct cluster, suggesting a recent emergence and spread of this variant. Our findings confirmed clonal transmission coupled with likely horizontal gene transfer in carbapenem-resistant Klebsiella pneumoniae ST14. Dissemination of this genetically flexible, highly resistant clone warrants further monitoring.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN38,

title = {A Stretch of Unpaired Purines in the Leader Region of Simian Immunodeficiency Virus (SIV) Genomic RNA is Critical for its Packaging into Virions},

author = {V. N. Pillai and L. M. Ali and S. G. Prabhu and A. Krishnan and A. Chameettachal and F. N. N. Pitchai and F. Mustafa and T. A. Rizvi},

doi = {10.1016/j.jmb.2021.167293},

issn = {0022-2836},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Mol Biol},

volume = {433},

number = {23},

pages = {167293},

abstract = {Simian immunodeficiency virus (SIV) is an important lentivirus used as a non-human primate model to study HIV replication, and pathogenesis of human AIDS, as well as a potential vector for human gene therapy. This study investigated the role of single-stranded purines (ssPurines) as potential genomic RNA (gRNA) packaging determinants in SIV replication. Similar ssPurines have been implicated as important motifs for gRNA packaging in many retroviruses like, HIV-1, MPMV, and MMTV by serving as Gag binding sites during virion assembly. In examining the secondary structure of the SIV 5' leader region, as recently deduced using SHAPE methodology, we identified four specific stretches of ssPurines (I-IV) in the region that harbors major packaging determinants of SIV. The significance of these ssPurine motifs were investigated by mutational analysis coupled with a biologically relevant single round of replication assay. These analyses revealed that while ssPurine II was essential, the others (ssPurines I, III, & IV) did not significantly contribute to SIV gRNA packaging. Any mutation in the ssPurine II, such as its deletion or substitution, or other mutations that caused base pairing of ssPurine II loop resulted in near abrogation of RNA packaging, further substantiating the crucial role of ssPurine II and its looped conformation in SIV gRNA packaging. Structure prediction analysis of these mutants further corroborated the biological results and further revealed that the unpaired nature of ssPurine II is critical for its function during SIV RNA packaging perhaps by enabling it to function as a specific binding site for SIV Gag.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN19,

title = {Identification of Pr78(Gag) Binding Sites on the Mason-Pfizer Monkey Virus Genomic RNA Packaging Determinants},

author = {F. N. N. Pitchai and A. Chameettachal and V. Vivet-Boudou and L. M. Ali and V. N. Pillai and A. Krishnan and S. Bernacchi and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1016/j.jmb.2021.166923},

issn = {0022-2836},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Mol Biol},

volume = {433},

number = {10},

pages = {166923},

abstract = {How retroviral Gag proteins recognize the packaging signals (Psi) on their genomic RNA (gRNA) is a key question that we addressed here using Mason-Pfizer monkey virus (MPMV) as a model system by combining band-shift assays and footprinting experiments. Our data show that Pr78(Gag) selects gRNA against spliced viral RNA by simultaneously binding to two single stranded loops on the MPMV Psi RNA: (1) a large purine loop (ssPurines), and (2) a loop which partially overlaps with a mostly base-paired purine repeat (bpPurines) and extends into a GU-rich binding motif. Importantly, this second Gag binding site is located immediately downstream of the major splice donor (mSD) and is thus absent from the spliced viral RNAs. Identifying elements crucial for MPMV gRNA packaging should help in understanding not only the mechanism of virion assembly by retroviruses, but also facilitate construction of safer retroviral vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN28,

title = {Simultaneous and rapid quantification of microalga biomolecule content using electrochemical impedance spectroscopy},

author = {M. Al Ahmad and S. Raji and F. Mustafa and T. A. Rizvi and S. Al-Zuhair},

doi = {10.1002/btpr.3037},

issn = {1520-6033},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Biotechnol Prog},

volume = {36},

number = {6},

pages = {e3037},

abstract = {Lipids, proteins, and carbohydrates are the major constituents found in microalga cells, in varying proportions, and these biomolecules find applications in different industries. During microalga cultivation, to efficiently manipulate, control, and optimize the productivity of a specific compound for a specific application, real-time monitoring of these three cell components is essential. In this study, a method using measurement of electrical capacitance was developed to simultaneously determine the lipid, protein, and carbohydrate content of microalga cells without the requirement for any pre-processing steps. The marine microalga Nannochloropsis oculata was cultivated under nitrogen starvation conditions to induce lipid accumulation over a period of 22 days. The correlation between the electrical capacitance of the microalga culture and the intracellular biomolecule content (determined by standard techniques) was investigated, enabling subsequent deduction of microalga intracellular content from electrical capacitance of the culture. The accuracy and precision of the technique were proven by validating an independent sample. The main advantage of the proposed technique is its capability of quantifying microalga composition within a few minutes, significantly faster than currently available conventional techniques.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN36,

title = {Role of Purine-Rich Regions in Mason-Pfizer Monkey Virus (MPMV) Genomic RNA Packaging and Propagation},

author = {L. M. Ali and F. N. N. Pitchai and V. Vivet-Boudou and A. Chameettachal and A. Jabeen and V. N. Pillai and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.3389/fmicb.2020.595410},

issn = {1664-302X (Print) 1664-302x},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Front Microbiol},

volume = {11},

pages = {595410},

abstract = {A distinguishing feature of the Mason-Pfizer monkey virus (MPMV) packaging signal RNA secondary structure is a single-stranded purine-rich sequence (ssPurines) in close vicinity to a palindromic stem loop (Pal SL) that functions as MPMV dimerization initiation site (DIS). However, unlike other retroviruses, MPMV contains a partially base-paired repeat sequence of ssPurines (bpPurines) in the adjacent region. Both purine-rich sequences have earlier been proposed to act as potentially redundant Gag binding sites to initiate the process of MPMV genomic RNA (gRNA) packaging. The objective of this study was to investigate the biological significance of ssPurines and bpPurines in MPMV gRNA packaging by systematic mutational and biochemical probing analyses. Deletion of either ssPurines or bpPurines individually had no significant effect on MPMV gRNA packaging, but it was severely compromised when both sequences were deleted simultaneously. Selective 2' hydroxyl acylation analyzed by primer extension (SHAPE) analysis of the mutant RNAs revealed only mild effects on structure by deletion of either ssPurines or bpPurines, while the structure was dramatically affected by the two simultaneous deletions. This suggests that ssPurines and bpPurines play a redundant role in MPMV gRNA packaging, probably as Gag binding sites to facilitate gRNA capture and encapsidation. Interestingly, the deletion of bpPurines revealed an additional severe defect on RNA propagation that was independent of the presence or absence of ssPurines or the gRNA structure of the region. These findings further suggest that the bpPurines play an additional role in the early steps of MPMV replication cycle that is yet to be identified.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN22,

title = {Electrical detection of blood cells in urine},

author = {N. Nasir and S. Raji and F. Mustafa and T. A. Rizvi and Z. Al Natour and A. Hilal-Alnaqbi and M. Al Ahmad},

doi = {10.1016/j.heliyon.2019.e03102},

issn = {2405-8440 (Print) 2405-8440},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Heliyon},

volume = {6},

number = {1},

pages = {e03102},

abstract = {Available methods for detecting blood in the urine (hematuria) can be problematic since results can be influenced by many factors in patients and in the lab settings, resulting in false positive or false negative results. This necessitates the development of new, accurate and easy-access methods that save time and effort. This study demonstrates a label-free and accurate method for detecting the presence of red and white blood cells (RBCs and WBCs) in urine by measuring the changes in the dielectric properties of urine upon increasing concentrations of both cell types. The current method could detect changes in the electrical properties of fresh urine over a short time interval, making this method suitable for detecting changes that cannot be recognized by conventional methods. Correcting for these changes enabled the detection of a minimum cell concentration of 10(2) RBCs per ml which is not possible by conventional methods used in the labs except for the semi-quantitative method that can detect 50 RBCs per ml, but it is a lengthy and involved procedure, not suitable for high volume labs. This ability to detect very small amount of both types of cells makes the proposed technique an attractive tool for detecting hematuria, the presence of which is indicative of problems in the excretory system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN81,

title = {In vitro efficacy of ceftazidime-avibactam, aztreonam-avibactam and other rescue antibiotics against carbapenem-resistant Enterobacterales from the Arabian Peninsula},

author = {Á Sonnevend and A. Ghazawi and D. Darwish and G. Barathan and R. Hashmey and T. Ashraf and T. A. Rizvi and T. Pál},

doi = {10.1016/j.ijid.2020.07.050},

issn = {1201-9712},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Int J Infect Dis},

volume = {99},

pages = {253-259},

abstract = {OBJECTIVES: Our aim was to assess the susceptibility of carbapenem-resistant Enterobacterales (CRE) from the Arabian Peninsula to a broad spectrum of antibiotics, including fosfomycin, ceftazidime-avibactam, and aztreonam-avibactam. METHODS: 1192 non-repeat CRE isolated in 2009-2017 from 33 hospitals in five countries of the Arabian Peninsula were tested. The minimum inhibitory concentration of 14 antibiotics was determined. Carbapenemase and 16S methylase genes were detected by PCR. Clonality was assessed by PFGE. RESULTS: The highest rate of susceptibility was detected to aztreonam-avibactam (95.5%) followed by colistin (79.8%), fosfomycin (71.8%) and tigecycline (59.9%). Isolates co-producing two carbapenemases (12.4%) were the least susceptible. Aminoglycoside susceptibility was affected by the frequent production of a 16S methylase. Susceptibility to ceftazidime-avibactam was impacted by the high rate of metallo-beta-lactamase producers (46.3%), while aztreonam-avibactam resistance occurred mostly in clonally unrelated, carbapenemase non-producing Escherichia coli. CONCLUSION: Of the currently available drugs: colistin, tigecycline, and ceftazidime-avibactam co-administered with aztreonam appear to be the most effective to treat CRE infections. However, the presence of non-clonal CRE isolates, in which avibactam does not lower the aztreonam MIC below the clinical breakpoint, is of notable concern. Based on the relatively high rate of fosfomycin susceptibility, it would be desirable to license parenteral fosfomycin in the region.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN41,

title = {The Large Action of Chlorpromazine: Translational and Transdisciplinary Considerations in the Face of COVID-19},

author = {E. Stip and T. A. Rizvi and F. Mustafa and S. Javaid and S. Aburuz and N. N. Ahmed and K. Abdel Aziz and D. Arnone and A. Subbarayan and F. Al Mugaddam and G. Khan},

doi = {10.3389/fphar.2020.577678},

issn = {1663-9812 (Print) 1663-9812},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Front Pharmacol},

volume = {11},

pages = {577678},

abstract = {Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome (SARS) in humans that is caused by SARS-associated coronavirus type 2 (SARS-CoV-2). In the context of COVID-19, several aspects of the relations between psychiatry and the pandemic due to the coronavirus have been described. Some drugs used as antiviral medication have neuropsychiatric side effects, and conversely some psychotropic drugs have antiviral properties. Chlorpromazine (CPZ, Largactil(®)) is a well-established antipsychotic medication that has recently been proposed to have antiviral activity against SARS-CoV-2. This review aims to 1) inform health care professionals and scientists about the history of CPZ use in psychiatry and its potential anti- SARS-CoV-2 activities 2) inform psychiatrists about its potential anti-SARS-CoV-2 activities, and 3) propose a research protocol for investigating the use of CPZ in the treatment of COVID-19 during the potential second wave. The history of CPZ's discovery and development is described in addition to the review of literature from published studies within the discipline of virology related to CPZ. The early stages of infection with coronavirus are critical events in the course of the viral cycle. In particular, viral entry is the first step in the interaction between the virus and the cell that can initiate, maintain, and spread the infection. The possible mechanism of action of CPZ is related to virus cell entry via clathrin-mediated endocytosis. Therefore, CPZ could be useful to treat COVID-19 patients provided that its efficacy is evaluated in adequate and well-conducted clinical trials. Interestingly, clinical trials of very good quality are in progress. However, more information is still needed about the appropriate dosage regimen. In short, CPZ repositioning is defined as a new use beyond the field of psychiatry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN9,

title = {SARS-CoV-2/COVID-19: Viral Genomics, Epidemiology, Vaccines, and Therapeutic Interventions},

author = {M. Uddin and F. Mustafa and T. A. Rizvi and T. Loney and H. A. Suwaidi and A. H. H. Al-Marzouqi and A. K. Eldin and N. Alsabeeha and T. E. Adrian and C. Stefanini and N. Nowotny and A. Alsheikh-Ali and A. C. Senok},

doi = {10.3390/v12050526},

issn = {1999-4915},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Viruses},

volume = {12},

number = {5},

abstract = {The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 virus that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress, and fatality. To address this global crisis, up-to-date information on viral genomics and transcriptomics is crucial for understanding the origins and global dispersion of the virus, providing insights into viral pathogenicity, transmission, and epidemiology, and enabling strategies for therapeutic interventions, drug discovery, and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Krishnan2019,

title = {Purification and Functional Characterization of a Biologically Active Full-Length Feline Immunodeficiency Virus (FIV) Pr50Gag},

author = {A. Krishnan and Vineeta N. Pillai and Akhil Chameettachal and Lizna Mohamed Ali and Fathima Nuzra Nagoor Pitchai and Saeed Tariq and Farah Mustafa and Roland Marquet and Tahir A. Rizvi},

doi = {10.3390/v11080689},

issn = {1999-4915},

year  = {2019},

date = {2019-08-00},

urldate = {2019-08-00},

journal = {Viruses},

volume = {11},

number = {8},

publisher = {MDPI AG},

abstract = {<jats:p>The feline immunodeficiency virus (FIV) full-length Pr50Gag precursor is a key player in the assembly of new viral particles. It is also a critical component of the efficient selection and packaging of two copies of genomic RNA (gRNA) into the newly formed virus particles from a wide pool of cellular and spliced viral RNA. To understand the molecular mechanisms involved during FIV gRNA packaging, we expressed the His6-tagged and untagged recombinant FIV Pr50Gag protein both in eukaryotic and prokaryotic cells. The recombinant Pr50Gag-His6-tag fusion protein was purified from soluble fractions of prokaryotic cultures using immobilized metal affinity chromatography (IMAC). This purified protein was able to assemble in vitro into virus-like particles (VLPs), indicating that it preserved its ability to oligomerize/multimerize. Furthermore, VLPs formed in eukaryotic cells by the FIV full-length Pr50Gag both in the presence and absence of His6-tag could package FIV sub-genomic RNA to similar levels, suggesting that the biological activity of the recombinant full-length Pr50Gag fusion protein was retained in the presence of His6-tag at the carboxy terminus. Successful expression and purification of a biologically active, recombinant full-length Pr50Gag-His6-tag fusion protein will allow study of the intricate RNA-protein interactions involved during FIV gRNA encapsidation.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN53,

title = {Stabilizing role of structural elements within the 5´ Untranslated Region (UTR) and gag sequences in Mason-Pfizer monkey virus (MPMV) genomic RNA packaging},

author = {R. M. Kalloush and V. Vivet-Boudou and L. M. Ali and V. N. Pillai and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1080/15476286.2019.1572424},

issn = {1547-6286 (Print) 1547-6286},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {RNA Biol},

volume = {16},

number = {5},

pages = {612-625},

abstract = {The Mason-Pfizer monkey virus (MPMV) genomic RNA (gRNA) packaging signal is a highly-structured element with several stem-loops held together by two phylogenetically conserved long-range interactions (LRIs) between U5 and gag complementary sequences. These LRIs play a critical role in maintaining the structure of the 5´ end of the MPMV gRNA. Thus, one could hypothesize that the overall RNA secondary structure of this region is further architecturally held together by three other stem loops (SL3, Gag SL1, and Gag SL2) comprising of sequences from the distal parts of the 5´untranslated region (5' UTR) to ~ 120 nucleotides into gag, excluding gag sequences involved in forming the U5-Gag LRIs. To provide functional evidence for the biological significance of these stem loops during gRNA encapsidation, these structural motifs were mutated and their effects on MPMV RNA packaging and propagation were tested in a single round trans-complementation assay. The mutant RNA structures were further studied by high throughput SHAPE (hSHAPE) assay. Our results reveal that sequences involved in forming these three stem loops do not play crucial roles at an individual level during MPMV gRNA packaging or propagation. Further structure-function analysis indicates that the U5-Gag LRIs have a more important architectural role in stabilizing the higher order structure of the 5´ UTR than the three stem loops which have a more secondary and perhaps indirect role in stabilizing the overall RNA secondary structure of the region. Our work provides a better understanding of the molecular interactions that take place during MPMV gRNA packaging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN32,

title = {A cis-Acting Element Downstream of the Mouse Mammary Tumor Virus Major Splice Donor Critical for RNA Elongation and Stability},

author = {S. Akhlaq and N. G. Panicker and P. S. Philip and L. M. Ali and J. P. Dudley and T. A. Rizvi and F. Mustafa},

doi = {10.1016/j.jmb.2018.08.025},

issn = {0022-2836 (Print) 0022-2836},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {J Mol Biol},

volume = {430},

number = {21},

pages = {4307-4324},

abstract = {BACKGROUND: The mouse mammary tumor virus (MMTV) encodes a functional signal peptide, a cleavage product of envelope and Rem proteins. Signal peptide interacts with a 3' cis-acting RNA element, the Rem-responsive element (RmRE), to facilitate expression of both unspliced genomic (gRNA) and spliced mRNAs. An additional RmRE has been proposed at the 5' end of the genome, facilitating nuclear export of the unspliced gRNA, whereas the 3' RmRE could facilitate translation of all other mRNAs, including gRNA. RESULTS: To address this hypothesis, a series of mutations were introduced into a 24-nt region found exclusively in the unspliced gRNA. Mutant clones using MMTV or human cytomegalovirus promoters were tested in both transient and stable transfections to determine their effect on gRNA nuclear export, stability, and translation. Nuclear export of the gRNA was affected only in a small mutant subset in stably transfected Jurkat T cells. Quantitative real-time RT-PCR of actinomycin D-treated cells expressing MMTV revealed that multiple mutants were severely compromised for RNA expression and stability. Both genomic and spliced nuclear RNAs were reduced, leading to abrogation of Gag and Env protein expressed from unspliced and spliced mRNAs, respectively. RT-PCRs with multiple primer pairs indicated failure to elongate genomic MMTV transcripts beyond ~500 nt compared to the wild type in a cell line-dependent manner. CONCLUSIONS: MMTV contains a novel cis-acting element downstream of the major splice donor critical for facilitating MMTV gRNA elongation and stability. Presence of a mirror repeat within the element may represent important viral/host factor binding site(s) within MMTV gRNA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN88,

title = {Biochemical and Functional Characterization of Mouse Mammary Tumor Virus Full-Length Pr77(Gag) Expressed in Prokaryotic and Eukaryotic Cells},

author = {A. Chameettachal and V. N. Pillai and L. M. Ali and F. N. N. Pitchai and M. T. Ardah and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.3390/v10060334},

issn = {1999-4915},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {Viruses},

volume = {10},

number = {6},

abstract = {The mouse mammary tumor virus (MMTV) Pr77(Gag) polypeptide is an essential retroviral structural protein without which infectious viral particles cannot be formed. This process requires specific recognition and packaging of dimerized genomic RNA (gRNA) by Gag during virus assembly. Most of the previous work on retroviral assembly has used either the nucleocapsid portion of Gag, or other truncated Gag derivatives—not the natural substrate for virus assembly. In order to understand the molecular mechanism of MMTV gRNA packaging process, we expressed and purified full-length recombinant Pr77(Gag)-His₆-tag fusion protein from soluble fractions of bacterial cultures. We show that the purified Pr77(Gag)-His₆-tag protein retained the ability to assemble virus-like particles (VLPs) in vitro with morphologically similar immature intracellular particles. The recombinant proteins (with and without His₆-tag) could both be expressed in prokaryotic and eukaryotic cells and had the ability to form VLPs in vivo. Most importantly, the recombinant Pr77(Gag)-His₆-tag fusion proteins capable of making VLPs in eukaryotic cells were competent for packaging sub-genomic MMTV RNAs. The successful expression and purification of a biologically active, full-length MMTV Pr77(Gag) should lay down the foundation towards performing RNA–protein interaction(s), especially for structure-function studies and towards understanding molecular intricacies during MMTV gRNA packaging and assembly processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN90,

title = {The bifurcated stem loop 4 (SL4) is crucial for efficient packaging of mouse mammary tumor virus (MMTV) genomic RNA},

author = {F. Mustafa and V. Vivet-Boudou and A. Jabeen and L. M. Ali and R. M. Kalloush and R. Marquet and T. A. Rizvi},

doi = {10.1080/15476286.2018.1486661},

issn = {1547-6286 (Print) 1547-6286},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {RNA Biol},

volume = {15},

number = {8},

pages = {1047-1059},

abstract = {Packaging the mouse mammary tumor virus (MMTV) genomic RNA (gRNA) requires the entire 5' untranslated region (UTR) in conjunction with the first 120 nucleotides of the gag gene. This region includes several palindromic (pal) sequence(s) and stable stem loops (SLs). Among these, stem loop 4 (SL4) adopts a bifurcated structure consisting of three stems, two apical loops, and an internal loop. Pal II, located in one of the apical loops, mediates gRNA dimerization, a process intricately linked to packaging. We thus hypothesized that the bifurcated SL4 structure could constitute the major gRNA packaging determinant. To test this hypothesis, the two apical loops and the flanking sequences forming the bifurcated SL4 were individually mutated. These mutations all had deleterious effects on gRNA packaging and propagation. Next, single and compensatory mutants were designed to destabilize then recreate the bifurcated SL4 structure. A structure-function analysis using bioinformatics predictions and RNA chemical probing revealed that mutations that led to the loss of the SL4 bifurcated structure abrogated RNA packaging and propagation, while compensatory mutations that recreated the native SL4 structure restored RNA packaging and propagation to wild type levels. Altogether, our results demonstrate that SL4 constitutes the principal packaging determinant of MMTV gRNA. Our findings further suggest that SL4 acts as a structural switch that can not only differentiate between RNA for translation versus packaging/dimerization, but its location also allows differentiation between spliced and unspliced RNAs during gRNA encapsidation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN51,

title = {Expression, purification, and characterization of biologically active full-length Mason-Pfizer monkey virus (MPMV) Pr78(Gag)},

author = {F. N. N. Pitchai and L. Ali and V. N. Pillai and A. Chameettachal and S. S. Ashraf and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1038/s41598-018-30142-0},

issn = {2045-2322},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {Sci Rep},

volume = {8},

number = {1},

pages = {11793},

abstract = {MPMV precursor polypeptide Pr78(Gag) orchestrates assembly and packaging of genomic RNA (gRNA) into virus particles. Therefore, we have expressed recombinant full-length Pr78(Gag) either with or without His(6)-tag in bacterial as well as eukaryotic cultures and purified the recombinant protein from soluble fractions of the bacterial cultures. The recombinant Pr78(Gag) protein has the intrinsic ability to assemble in vitro to form virus like particles (VLPs). Consistent with this observation, the recombinant protein could form VLPs in both prokaryotes and eukaryotes. VLPs formed in eukaryotic cells by recombinant Pr78(Gag) with or without His(6)-tag can encapsidate MPMV transfer vector RNA, suggesting that the inclusion of the His(6)-tag to the full-length Pr78(Gag) did not interfere with its expression or biological function. This study demonstrates the expression and purification of a biologically active, recombinant Pr78(Gag), which should pave the way to study RNA-protein interactions involved in the MPMV gRNA packaging process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{AlAhmad2018b,

title = {Electrical Characterization of Normal and Cancer Cells},

author = {Mahmoud Al Ahmad and Zeina Al Natour and Farah Mustafa and Tahir A. Rizvi},

doi = {10.1109/access.2018.2830883},

issn = {2169-3536},

year  = {2018},

date = {2018-00-00},

urldate = {2018-00-00},

journal = {IEEE Access},

volume = {6},

pages = {25979--25986},

publisher = {Institute of Electrical and Electronics Engineers (IEEE)},

abstract = {In this paper, we characterize and discriminate between normal and cancer cells from three different tissue types, liver, lung, and breast, using capacitance–voltage-based extracted set of parameters. Cells from each type of cancer cell line were suspended in a liquid media either individually or as mixtures with their normal counterparts. Empirically, normal cells were observed to exhibit higher dielectric constants when compared to cancer cells from the same tissue. Moreover, adding cancer cells to normal cells was observed to increase the capacitance of normal cells, and the extent of this increase varied with the type of tissue tested with the lung cells causing the greatest change. This shows that the cancer cells of different cell origin possess their own signature electrical parameters, especially when compared with their normal counterparts, and that cancer cell seems to affect normal cells in a different manner, depending upon the tissue type. It was also noticed that the cells (both cancer and normal) exhibited a higher dielectric value as per the following order (from least to most): breast, lung, and liver. The changes in electrical parameters from normal to cancer state were explained not only by the modification of its physiological and biochemical properties but also by the morphological changes. This approach paves the way for exploring unique electrical signatures of normal and their corresponding cancer cells to enable their detection and discrimination.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{AlAhmad2018,

title = {Detection of Mouse Mammary Tumor Virus (MMTV) Particles in an Immortalized T Cell Line Based on Electrical Parameters},

author = {Mahmoud Al Ahmad and Shaima Akhlaq and Tahir A. Rizvi and Farah Mustafa},

doi = {10.1109/access.2018.2874987},

issn = {2169-3536},

year  = {2018},

date = {2018-00-00},

urldate = {2018-00-00},

journal = {IEEE Access},

volume = {6},

pages = {63597--63605},

publisher = {Institute of Electrical and Electronics Engineers (IEEE)},

abstract = {Label-free detection and characterization of cells producing virus particles is a highly desirable property that can pave the way for direct detection of virally infected cells in body fluids, tissues, and eventually in infected individuals. Identification of such properties can also provide a better understanding of the growth and/or evolution of virally infected cells in real-time experimental setups. This paper takes a closer look at the electrical properties of an immortalized T cell line capable of producing virus particles along with its non-virus producing control cell line using capacitance-voltage (C-V) measurements. In addition, two other important control cell lines were also included in which the ability of the cells to produce virus particles was abrogated by using genetic mutations. The conducted C-V measurements revealed that it is possible to electrically differentiate between these different cell lines. The cells producing wild-type (WT) virus particles could be distinguished from the control cells in which no DNA was introduced and, hence, were incapable of producing any virus particles. Interestingly, the cells in which two mutant DNAs were introduced that abrogated their ability to produce virus particles showed a similar electrical profile to each other, yet distinct from that of the cells producing the WT virus. These results clearly demonstrate that the electrical technique was able to distinguish between cells expressing virus particles versus cells that do not express virus particles. Data analysis revealed a twofold difference in the interaction capacitance between WT and mutant cells. Characterizing cells using electrical parameters are not laborious and lengthy, as is the case with conventional biochemical methods that typically take several days. Together, these data suggest that it is possible to electrically characterize and differentiate virally infected cells from uninfected cells. It is our hope that eventually these observations co...},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN18,

title = {Electrical characterization of DNA supported on nitrocellulose membranes},

author = {M. A. Ahmad and R. M. Milhem and N. G. Panicker and T. A. Rizvi and F. Mustafa},

doi = {10.1038/srep29089},

issn = {2045-2322},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Sci Rep},

volume = {6},

pages = {29089},

abstract = {Integrated DNA-based nanoscale electronic devices will enable the continued realization of Moore's Law at the level of functional devices and systems. In this work, the electrical characterization of single and complementary base paired DNA has been directly measured and investigated via the use of nitrocellulose membranes. A radio frequency DAKS-3.5 was used to measure the reflection coefficients of different DNA solutions dotted onto nitrocellulose membranes. Each DNA solution was exposed to a radio frequency signal with a power of 10 dBm and with a sweep from 200 MHz up to 13.6 GHz. The conducted measurements show some distinctions between the homomeric and complementary bases due to their different electrical polarization. As revealed from the measurements conducted, with the addition of DNA oligonucleotides, the measured capacitance increased when compared with buffer medium alone. The DNA molecules could be modeled as dielectric material that can hold electrical charges. Furthermore, the complementary paired DNA molecule-based inks solutions had a higher capacitance value compared with single DNA molecules (A, C, G and T) solutions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN101,

title = {Electrical detection and quantification of single and mixed DNA nucleotides in suspension},

author = {M. A. Ahmad and N. G. Panicker and T. A. Rizvi and F. Mustafa},

doi = {10.1038/srep34016},

issn = {2045-2322},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Sci Rep},

volume = {6},

pages = {34016},

abstract = {High speed sequential identification of the building blocks of DNA, (deoxyribonucleotides or nucleotides for short) without labeling or processing in long reads of DNA is the need of the hour. This can be accomplished through exploiting their unique electrical properties. In this study, the four different types of nucleotides that constitute a DNA molecule were suspended in a buffer followed by performing several types of electrical measurements. These electrical parameters were then used to quantify the suspended DNA nucleotides. Thus, we present a purely electrical counting scheme based on the semiconductor theory that allows one to determine the number of nucleotides in a solution by measuring their capacitance-voltage dependency. The nucleotide count was observed to be similar to the multiplication of the corresponding dopant concentration and debye volume after de-embedding the buffer contribution. The presented approach allows for a fast and label-free quantification of single and mixed nucleotides in a solution.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN15,

title = {Cross- and Co-Packaging of Retroviral RNAs and Their Consequences},

author = {L. M. Ali and T. A. Rizvi and F. Mustafa},

doi = {10.3390/v8100276},

issn = {1999-4915},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Viruses},

volume = {8},

number = {10},

abstract = {Retroviruses belong to the family Retroviridae and are ribonucleoprotein (RNP) particles that contain a dimeric RNA genome. Retroviral particle assembly is a complex process, and how the virus is able to recognize and specifically capture the genomic RNA (gRNA) among millions of other cellular and spliced retroviral RNAs has been the subject of extensive investigation over the last two decades. The specificity towards RNA packaging requires higher order interactions of the retroviral gRNA with the structural Gag proteins. Moreover, several retroviruses have been shown to have the ability to cross-/co-package gRNA from other retroviruses, despite little sequence homology. This review will compare the determinants of gRNA encapsidation among different retroviruses, followed by an examination of our current understanding of the interaction between diverse viral genomes and heterologous proteins, leading to their cross-/co-packaging. Retroviruses are well-known serious animal and human pathogens, and such a cross-/co-packaging phenomenon could result in the generation of novel viral variants with unknown pathogenic potential. At the same time, however, an enhanced understanding of the molecular mechanisms involved in these specific interactions makes retroviruses an attractive target for anti-viral drugs, vaccines, and vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN77,

title = {Packaging of Mason-Pfizer monkey virus (MPMV) genomic RNA depends upon conserved long-range interactions (LRIs) between U5 and gag sequences},

author = {R. M. Kalloush and V. Vivet-Boudou and L. M. Ali and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1261/rna.055731.115},

issn = {1355-8382 (Print) 1355-8382},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Rna},

volume = {22},

number = {6},

pages = {905-19},

abstract = {MPMV has great potential for development as a vector for gene therapy. In this respect, precisely defining the sequences and structural motifs that are important for dimerization and packaging of its genomic RNA (gRNA) are of utmost importance. A distinguishing feature of the MPMV gRNA packaging signal is two phylogenetically conserved long-range interactions (LRIs) between U5 and gag complementary sequences, LRI-I and LRI-II. To test their biological significance in the MPMV life cycle, we introduced mutations into these structural motifs and tested their effects on MPMV gRNA packaging and propagation. Furthermore, we probed the structure of key mutants using SHAPE (selective 2'hydroxyl acylation analyzed by primer extension). Disrupting base-pairing of the LRIs affected gRNA packaging and propagation, demonstrating their significance to the MPMV life cycle. A double mutant restoring a heterologous LRI-I was fully functional, whereas a similar LRI-II mutant failed to restore gRNA packaging and propagation. These results demonstrate that while LRI-I acts at the structural level, maintaining base-pairing is not sufficient for LRI-II function. In addition, in vitro RNA dimerization assays indicated that the loss of RNA packaging in LRI mutants could not be attributed to the defects in dimerization. Our findings suggest that U5-gag LRIs play an important architectural role in maintaining the structure of the 5' region of the MPMV gRNA, expanding the crucial role of LRIs to the nonlentiviral group of retroviruses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN21,

title = {Label-free capacitance-based identification of viruses},

author = {M. Al Ahmad and F. Mustafa and L. M. Ali and J. V. Karakkat and T. A. Rizvi},

doi = {10.1038/srep09809},

issn = {2045-2322},

year  = {2015},

date = {2015-01-01},

urldate = {2015-01-01},

journal = {Sci Rep},

volume = {5},

pages = {9809},

abstract = {This study was undertaken to quantitate a single virus suspension in culture medium without any pre-processing. The electrical capacitance per virus particle was used to identify the kind of virus present by measuring the suspension (virus plus medium) capacitance, de-embedding the medium contribution, and dividing by the virus count. The proposed technique is based on finding the single virus effective dielectric constant which is directly related to the virus composition. This value was used to identify the virus type accordingly. Two types of viruses thus tested were further quantified by a biochemical technique to validate the results. Furthermore, non-organic nanoparticles with known concentration and capacitance per particle were identified using the proposed method. The selectivity of the method was demonstrated by performing electrical measurements on a third virus, revealing that the proposed technique is specific and sensitive enough to permit detection of a few hundred virus particles per milliliter within a few minutes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN117,

title = {Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells},

author = {M. Ali Khan and M. Kedhari Sundaram and A. Hamza and U. Quraishi and D. Gunasekera and L. Ramesh and P. Goala and U. Al Alami and M. Z. Ansari and T. A. Rizvi and C. Sharma and A. Hussain},

doi = {10.1155/2015/412149},

issn = {1741-427X (Print) 1741-427x},

year  = {2015},

date = {2015-01-01},

urldate = {2015-01-01},

journal = {Evid Based Complement Alternat Med},

volume = {2015},

pages = {412149},

abstract = {Sulforaphane (SFN) may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5 µM) for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RARβ, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs) was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs) and histone deacetylases (HDACs) were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time-dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN59,

title = {Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV)},

author = {S. J. Aktar and V. Vivet-Boudou and L. M. Ali and A. Jabeen and R. M. Kalloush and D. Richer and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1186/s12977-014-0096-6},

issn = {1742-4690},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {Retrovirology},

volume = {11},

pages = {96},

abstract = {BACKGROUND: One of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral gRNA in the form of a non-covalent RNA dimer by the assembling virions. It is becoming increasingly clear that the process of dimerization is closely linked with gRNA packaging, and in some retroviruses, the latter depends on the former. Earlier mutational analysis of the 5' end of the MMTV genome indicated that MMTV gRNA packaging determinants comprise sequences both within the 5' untranslated region (5' UTR) and the beginning of gag. RESULTS: The RNA secondary structure of MMTV gRNA packaging sequences was elucidated employing selective 2'hydroxyl acylation analyzed by primer extension (SHAPE). SHAPE analyses revealed the presence of a U5/Gag long-range interaction (U5/Gag LRI), not predicted by minimum free-energy structure predictions that potentially stabilizes the global structure of this region. Structure conservation along with base-pair covariations between different strains of MMTV further supported the SHAPE-validated model. The 5' region of the MMTV gRNA contains multiple palindromic (pal) sequences that could initiate intermolecular interaction during RNA dimerization. In vitro RNA dimerization, SHAPE analysis, and structure prediction approaches on a series of pal mutants revealed that MMTV RNA utilizes a palindromic point of contact to initiate intermolecular interactions between two gRNAs, leading to dimerization. This contact point resides within pal II (5' CGGCCG 3') at the 5' UTR and contains a canonical "GC" dyad and therefore likely constitutes the MMTV RNA dimerization initiation site (DIS). Further analyses of these pal mutants employing in vivo genetic approaches indicate that pal II, as well as pal sequences located in the primer binding site (PBS) are both required for efficient MMTV gRNA packaging. CONCLUSIONS: Employing structural prediction, biochemical, and genetic approaches, we show that pal II functions as a primary point of contact between two MMTV RNAs, leading to gRNA dimerization and its subsequent encapsidation into the assembling virus particles. The results presented here enhance our understanding of the MMTV gRNA dimerization and packaging processes and the role of structural motifs with respect to RNA-RNA and possibly RNA-protein interactions that might be taking place during MMTV life cycle.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN24,

title = {Virus detection and quantification using electrical parameters},

author = {M. Al Ahmad and F. Mustafa and L. M. Ali and T. A. Rizvi},

doi = {10.1038/srep06831},

issn = {2045-2322},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {Sci Rep},

volume = {4},

pages = {6831},

abstract = {Here we identify and quantitate two similar viruses, human and feline immunodeficiency viruses (HIV and FIV), suspended in a liquid medium without labeling, using a semiconductor technique. The virus count was estimated by calculating the impurities inside a defined volume by observing the change in electrical parameters. Empirically, the virus count was similar to the absolute value of the ratio of the change of the virus suspension dopant concentration relative to the mock dopant over the change in virus suspension Debye volume relative to mock Debye volume. The virus type was identified by constructing a concentration-mobility relationship which is unique for each kind of virus, allowing for a fast (within minutes) and label-free virus quantification and identification. For validation, the HIV and FIV virus preparations were further quantified by a biochemical technique and the results obtained by both approaches corroborated well. We further demonstrate that the electrical technique could be applied to accurately measure and characterize silica nanoparticles that resemble the virus particles in size. Based on these results, we anticipate our present approach to be a starting point towards establishing the foundation for label-free electrical-based identification and quantification of an unlimited number of viruses and other nano-sized particles.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN109,

title = {Ethanolic Neem (Azadirachta indica) Leaf Extract Prevents Growth of MCF-7 and HeLa Cells and Potentiates the Therapeutic Index of Cisplatin},

author = {C. Sharma and A. J. Vas and P. Goala and T. M. Gheewala and T. A. Rizvi and A. Hussain},

doi = {10.1155/2014/321754},

issn = {1687-8450 (Print) 1687-8450},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {J Oncol},

volume = {2014},

pages = {321754},

abstract = {The present study was designed to gain insight into the antiproliferative activity of ethanolic neem leaves extract (ENLE) alone or in combination with cisplatin by cell viability assay on human breast (MCF-7) and cervical (HeLa) cancer cells. Nuclear morphological examination and cell cycle analysis were performed to determine the mode of cell death. Further, to identify its molecular targets, the expression of genes involved in apoptosis, cell cycle progression, and drug metabolism was analyzed by RT-PCR. Treatment of MCF-7, HeLa, and normal cells with ENLE differentially suppressed the growth of cancer cells in a dose- and time-dependent manner through apoptosis. Additionally, lower dose combinations of ENLE with cisplatin resulted in synergistic growth inhibition of these cells compared to the individual drugs (combination index <1). ENLE significantly modulated the expression of bax, cyclin D1, and cytochrome P450 monooxygenases (CYP 1A1 and CYP 1A2) in a time-dependent manner in these cells. Conclusively, these results emphasize the chemopreventive ability of neem alone or in combination with chemotherapeutic treatment to reduce the cytotoxic effects on normal cells, while potentiating their efficacy at lower doses. Thus, neem may be a prospective therapeutic agent to combat gynecological cancers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}