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Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir

Waters et al., Environmental and Molecular Mutagenesis, doi:10.1002/em.22471
Jan 2022  
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Review of antiviral nucleoside analog drugs that induce lethal mutagenesis, including molnupiravir and favipiravir, and the potential mutagenic risks to human DNA and human mitochondrial DNA. Author recommends monitoring for mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity.
Reviews covering favipiravir for COVID-19 include1-4.
Study covers favipiravir and molnupiravir.
Waters et al., 28 Jan 2022, USA, peer-reviewed, 5 authors. Contact: mdwaters@centurylink.net, mdwatersalt@gmail.com.
This PaperFavipiravirAll
Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir
Michael D Waters, | Stafford Warren, Claude Hughes, Philip Lewis, Fengyu Zhang, Michael Waters Consulting
doi:10.22541/au.163603698.81246011/v1.
This review considers antiviral nucleoside analog (NA) drugs, including ribavirin, favipiravir, and molnupiravir, which induce genome error catastrophe in SARS-CoV or SARS-CoV-2 via lethal mutagenesis as a mode of action. In vitro data indicate that molnupiravir may be 100 times more potent as an antiviral agent than ribavirin or favipiravir. Molnupiravir has recently demonstrated efficacy in a phase 3 clinical trial. Because of its anticipated global use, its relative potency, and the reported in vitro "host" cell mutagenicity of its active principle, β-d-N4-hydroxycytidine, we have reviewed the development of molnupiravir and its genotoxicity safety evaluation, as well as the genotoxicity profiles of three congeners, that is, ribavirin, favipiravir, and 5-(2-chloroethyl)-2 0 -deoxyuridine. We consider the potential genetic risks of mol-
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