Pan-Viral Activity Landscape of Molnupiravir: Integrative Data Analysis Across RNA Virus Families and Experimental Systems
محل انتشار: مجله علوم دارویی و شیمی، دوره: 9، شماره: 3
سال انتشار: 1405
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 5
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شناسه ملی سند علمی:
JR_JMCH-9-3_008
تاریخ نمایه سازی: 17 بهمن 1404
چکیده مقاله:
Emerging and re-emerging RNA viruses continue to pose global health threats, highlighting the need for broad-spectrum antivirals that can be rapidly deployed against diverse viral families. Molnupiravir, a nucleoside analog that induces lethal mutagenesis, has shown promise as a broad-spectrum antiviral; yet, its efficacy across virus families remains incompletely mapped. This study systematically profiles the published antiviral activity of molnupiravir across all available virus families, genome types, and experimental systems, aiming to clarify determinants of susceptibility and to identify critical data gaps. A meta-analytic extraction and harmonization of all published EC۵۰/IC۵۰ values were performed, including assay metadata and comparator drugs where available. Statistical analyses and hierarchical clustering were used to visualize potency, breadth, and functional groupings across the viral landscape. The dataset comprises over ۶۰ unique data points covering ۱۳ virus families, with the most robust evidence for Coronaviridae, Orthomyxoviridae, and Togaviridae. Respiratory viruses, including SARS-CoV-۲, influenza, and RSV, showed exceptional sensitivity (median EC۵۰<۱ μM), while some flaviviruses and filoviruses were less susceptible. Potency was strongly influenced by both viral genome type and experimental system, with cell type and assay selection producing up to ۱۰-fold variation in reported EC۵۰. Head-to-head analysis demonstrated superior or equivalent potency of molnupiravir compared to remdesivir, favipiravir, and ribavirin across key viral families. Hierarchical clustering revealed that mechanistic susceptibility often transcends strict taxonomic boundaries, suggesting conserved determinants of drug action. Critical research gaps persist for several important families, including Bunyavirales and Arenaviridae. This comprehensive mapping provides a foundational resource for pandemic preparedness, rational antiviral stockpiling, and future drug development targeting broad viral threats.
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نویسندگان
Fredmoore L Orosco
Department of Biology, College of Science, University of the Philippines Manila, Metro Manila, Philippines
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