{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:51:08Z","timestamp":1792266668991,"version":"4.4.0"},"reference-count":152,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T00:00:00Z","timestamp":1650240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia e Innovaci\u00f3n (Spain)","award":["PID2019-104176RB-I00\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-104176RB-I00\/AEI\/10.13039\/501100011033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In RNA viruses, a small increase in their mutation rates can be sufficient to exceed their threshold of viability. Lethal mutagenesis is a therapeutic strategy based on the use of mutagens, driving viral populations to extinction. Extinction catastrophe can be experimentally induced by promutagenic nucleosides in cell culture models. The loss of HIV infectivity has been observed after passage in 5-hydroxydeoxycytidine or 5,6-dihydro-5-aza-2\u2032-deoxycytidine while producing a two-fold increase in the viral mutation frequency. Among approved nucleoside analogs, experiments with polioviruses and other RNA viruses suggested that ribavirin can be mutagenic, although its mechanism of action is not clear. Favipiravir and molnupiravir exert an antiviral effect through lethal mutagenesis. Both drugs are broad-spectrum antiviral agents active against RNA viruses. Favipiravir incorporates into viral RNA, affecting the G\u2192A and C\u2192U transition rates. Molnupiravir (a prodrug of \u03b2-d-N4-hydroxycytidine) has been recently approved for the treatment of SARS-CoV-2 infection. Its triphosphate derivative can be incorporated into viral RNA and extended by the coronavirus RNA polymerase. Incorrect base pairing and inefficient extension by the polymerase promote mutagenesis by increasing the G\u2192A and C\u2192U transition frequencies. Despite having remarkable antiviral action and resilience to drug resistance, carcinogenic risks and genotoxicity are important concerns limiting their extended use in antiviral therapy.<\/jats:p>","DOI":"10.3390\/v14040841","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T02:04:22Z","timestamp":1650420262000},"page":"841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-7976","authenticated-orcid":false,"given":"Ikbel","family":"Hadj Hassine","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Recherche UR17ES30 \u201cG\u00e9nomique, Biotechnologie et Strat\u00e9gies Antivirales\u201d, Institut Sup\u00e9rieur de Biotechnologie, Universit\u00e9 de Monastir, Monastir 5000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0145-7240","authenticated-orcid":false,"given":"Manel","family":"Ben M\u2019hadheb","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche UR17ES30 \u201cG\u00e9nomique, Biotechnologie et Strat\u00e9gies Antivirales\u201d, Institut Sup\u00e9rieur de Biotechnologie, Universit\u00e9 de Monastir, Monastir 5000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-6640","authenticated-orcid":false,"given":"Luis","family":"Men\u00e9ndez-Arias","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular \u201cSevero Ochoa\u201d (Consejo Superior de Investigaciones Cient\u00edficas & Universidad Aut\u00f3noma de Madrid), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9733","DOI":"10.1128\/JVI.00694-10","article-title":"Viral mutation rates","volume":"84","author":"Nebot","year":"2010","journal-title":"J. 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