{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T20:09:35Z","timestamp":1769976575705,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Molnupiravir, an oral direct\u2010acting antiviral effective in vitro against SARS\u2010CoV\u20102, has been largely employed during the COVID\u201019 pandemic, since December 2021. After marketing and widespread usage, a progressive increase in SARS\u2010CoV\u20102 lineages characterized by a higher transition\/transversion ratio, a characteristic signature of molnupiravir action, appeared in the Global Initiative on Sharing All Influenza Data\u00a0(GISAID) and International Nucleotide Sequence Database Collaboration\u00a0(INSDC) databases. Here, we assessed the drug effects by SARS\u2010CoV\u20102 whole\u2010genome sequencing on 38 molnupiravir\u2010treated persistently positive COVID\u201019 outpatients tested before and after treatment. Seventeen tixagevimab\/cilgavimab\u2010treated outpatients served as controls. Mutational analyses confirmed that SARS\u2010CoV\u20102 exhibits an increased transition\/transversion ratio seven days after initiation of molnupiravir. Moreover we observed an increased G\u2010&gt;A ratio compared to controls, which was not related to apolipoprotein B mRNAediting enzyme, catalytic polypeptide\u2010like (APOBEC) activity. In addition, we demonstrated for the first time an increased diversity and complexity of the viral quasispecies.<\/jats:p>","DOI":"10.1002\/jmv.29642","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T06:40:21Z","timestamp":1714977621000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molnupiravir increases SARS\u2010CoV\u20102 genome diversity and complexity: A case\u2010control cohort study"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8831-3380","authenticated-orcid":false,"given":"Cesare Ernesto Maria","family":"Gruber","sequence":"first","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio Giovanni","family":"Tucci","sequence":"additional","affiliation":[{"name":"Department of Biology University of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Giombini","sequence":"additional","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-7504","authenticated-orcid":false,"given":"Valentina","family":"Mazzotta","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Diseases Department National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro Giorgio","family":"Spezia","sequence":"additional","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5162-046X","authenticated-orcid":false,"given":"Martina","family":"Rueca","sequence":"additional","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Mastrorosa","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Diseases Department National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lavinia","family":"Fabeni","sequence":"additional","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Berno","sequence":"additional","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ornella","family":"Butera","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Rosati","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Diseases Department National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliana","family":"Specchiarello","sequence":"additional","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Carletti","sequence":"additional","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8811-195X","authenticated-orcid":false,"given":"Daniele","family":"Focosi","sequence":"additional","affiliation":[{"name":"North\u2010Western Tuscany Blood Bank Pisa University Hospital Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Nicastri","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Diseases Department National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Girardi","sequence":"additional","affiliation":[{"name":"Scientific Direction National Institute for Infectious Diseases \u201cL. Spallanzani\u201d\u2014IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Antinori","sequence":"additional","affiliation":[{"name":"Clinical and Research Infectious Diseases Department National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Maggi","sequence":"additional","affiliation":[{"name":"Laboratory of Virology National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Fact sheet for healthcare providers: emergency use authorization for Lagevrio\u2122 (molnupiravir) capsules. 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Effect of molnupiravir on SARS\u2010CoV\u20102 evolution in immunocompromised patients: a retrospective observational study.\u00a0Lancet Microbe. Published online March 22 2024.\u00a0doi:10.1016\/S2666-5247(23)00393-2","DOI":"10.1016\/S2666-5247(23)00393-2"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2016.03.017"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/v14091999"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2196\/31536"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp373"},{"key":"e_1_2_10_29_1","unstructured":"UK Health Security Agency. England COVID19 (Coronavirus) Dashboard-Potential MOV sequences. 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The effect of molnupiravir and nirmatrelvir on SARS\u2010CoV\u20102 genome diversity in infected and immune suppressed mice.\u00a0bioRxiv.\u00a0Preprint posted online February 28 2024.doi:10.1101\/2024.02.27.582110","DOI":"10.1128\/spectrum.01829-24"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.29642","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T06:41:17Z","timestamp":1757313677000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.29642"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/jmv.29642"],"URL":"https:\/\/doi.org\/10.1002\/jmv.29642","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2024-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29642"}}