{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:13:48Z","timestamp":1788261228999,"version":"build-2803163510"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":161,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00034\/1 MC_UU_12014"],"award-info":[{"award-number":["MC_UU_00034\/1 MC_UU_12014"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00034\/1 MC_UU_12014"],"award-info":[{"award-number":["MC_UU_00034\/1 MC_UU_12014"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutagenic antiviral drugs have shown promise against multiple viruses, but concerns have been raised about whether their use might promote the emergence of new and harmful viral variants. Recently, genetic signatures associated with molnupiravir use have been identified in the global SARS-COV-2 population. Here, we examine the consequences of using favipiravir and molnupiravir to treat SARS-CoV-2 infection in a hamster model, comparing viral genome sequence data collected from (1) untreated hamsters, and (2) from hamsters receiving effective and suboptimal doses of treatment. We identify a broadly linear relationship between drug dose and the extent of variation in treated viral populations, with a high proportion of this variation being composed of variants at frequencies of less than 1 per cent, below typical thresholds for variant calling. Treatment with an effective dose of antiviral drug was associated with a gain of between 7 and 10 variants per viral genome relative to drug-free controls: even after a short period of treatment a population founded by a transmitted virus could contain multiple sequence differences to that of the original host. Treatment with a suboptimal dose of drug showed intermediate gains of variants. No dose-dependent signal was identified in the numbers of single-nucleotide variants reaching frequencies in excess of 5\u2009per cent. We did not find evidence to support the emergence of drug resistance or of novel immune phenotypes. Our study suggests that where onward transmission occurs, a short period of treatment with mutagenic drugs may be sufficient to generate a significant increase in the number of viral variants transmitted.<\/jats:p>","DOI":"10.1093\/ve\/veae001","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T09:32:59Z","timestamp":1704274379000},"source":"Crossref","is-referenced-by-count":11,"title":["Genetic consequences of effective and suboptimal dosing with mutagenic drugs in a hamster model of SARS-CoV-2 infection"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0030-2784","authenticated-orcid":false,"given":"Christopher J. R","family":"Illingworth","sequence":"first","affiliation":[{"name":"MRC-University of Glasgow Centre for Virus Research , 464 Bearsden Road, Glasgow G61 1QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A","family":"Guerra-Assuncao","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital for Children NHS Foundation Trust , Great Ormond Street, London WC1N 3JH, UK"},{"name":"Infection, Immunity and Inflammation Research and Teaching Department, University College London , Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9655-7801","authenticated-orcid":false,"given":"Samuel","family":"Gregg","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Research and Teaching Department, University College London , Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Charles","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital for Children NHS Foundation Trust , Great Ormond Street, London WC1N 3JH, UK"},{"name":"Infection, Immunity and Inflammation Research and Teaching Department, University College London , Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-5903","authenticated-orcid":false,"given":"Juanita","family":"Pang","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Research and Teaching Department, University College London , Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunando","family":"Roy","sequence":"additional","affiliation":[{"name":"Infection, Immunity and Inflammation Research and Teaching Department, University College London , Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Abdelnabi","sequence":"additional","affiliation":[{"name":"KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy , Herestraat 49, Leuven B-3000, Belgium"},{"name":"The VirusBank Platform , Gaston Geenslaan, Leuven B-3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Neyts","sequence":"additional","affiliation":[{"name":"KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy , Herestraat 49, Leuven B-3000, Belgium"},{"name":"The VirusBank Platform , Gaston Geenslaan, Leuven B-3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Breuer","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital for Children NHS Foundation Trust , Great Ormond Street, London WC1N 3JH, UK"},{"name":"Infection, Immunity and Inflammation Research and Teaching Department, University College London , Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,4]]},"reference":[{"key":"2024061512205055300_R1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/infdis\/jiab361","article-title":"Molnupiravir Inhibits Replication of the Emerging SARS-CoV-2 Variants of Concern in a Hamster Infection Model","volume":"224","author":"Abdelnabi","year":"2021","journal-title":"The Journal of Infectious Diseases"},{"key":"2024061512205055300_R8","article-title":"The Combined Treatment of Molnupiravir and Favipiravir Results in a Potentiation of Antiviral Efficacy in a SARS-CoV-2 Hamster Infection Model","volume":"72","year":"2021","journal-title":"eBioMedicine"},{"key":"2024061512205055300_R2","doi-asserted-by":"crossref","first-page":"e01348","DOI":"10.1128\/JVI.01348-19","article-title":"Small-Molecule Antiviral \u03b2- D - N 4 -hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance","volume":"93","author":"Agostini","year":"2019","journal-title":"Journal of Virology"},{"key":"2024061512205055300_R3","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-022-04322-8","article-title":"A Proof-of-concept Study on the Genomic Evolution of Sars-Cov-2 in Molnupiravir-treated, Paxlovid-treated and Drug-na\u00efve Patients","volume":"5","author":"Alteri","year":"2022","journal-title":"Communications Biology"},{"key":"2024061512205055300_R4","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.57309","article-title":"SARS-CoV-2 (COVID-19) by the 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