{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:16:26Z","timestamp":1772997386103,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","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":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutations associated with severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) resistance to antiprotease nirmatrelvir were reported. We aimed to detect them in SARS\u2010CoV\u20102 genomes and quasispecies retrieved in our institute before drug availability in January 2022 and to analyze the impact of mutations on protease (3CLpro) structure. We sought for 38 3CLpro nirmatrelvir resistance mutations in a set of 62\u2009673 SARS\u2010CoV\u20102 genomes obtained in our institute from respiratory samples collected between 2020 and 2023 and for these mutations in SARS\u2010CoV\u20102 quasispecies for 90 samples collected in 2020, using Python. SARS\u2010CoV\u20102 protease with major mutation E166V was generated with Swiss Pdb Viewer and Molegro Molecular Viewer. We detected 22 (58%) of the resistance\u2010associated mutations in 417 (0.67%) of the genomes analyzed; 325 (78%) of these genomes had been obtained from samples collected in 2020\u22122021. APOBEC signatures were found for 12\/22 mutations. We also detected among viral quasispecies from 90 samples some minority reads harboring any of 15 nirmatrelvir resistance mutations, including E166V. Also, we predicted that E166V has a very limited effect on 3CLpro structure but may prevent drug attachment. Thus, we evidenced that mutations associated with nirmatrelvir resistance pre\u2010existed in SARS\u2010CoV\u20102 before drug availability. These findings further warrant SARS\u2010CoV\u20102 genomic surveillance and SARS\u2010CoV\u20102 quasispecies characterization.<\/jats:p>","DOI":"10.1002\/jmv.29462","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T06:58:18Z","timestamp":1708066698000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["EXPRESSION OF CONCERN: Resistance\u2010associated mutations to the anti\u2010SARS\u2010CoV\u20102 agent nirmatrelvir: Selection not induction"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-0308","authenticated-orcid":false,"given":"Philippe","family":"Colson","sequence":"first","affiliation":[{"name":"IHU M\u00e9diterran\u00e9e Infection 19\u201021 boulevard Jean Moulin  Marseille France"},{"name":"Aix\u2010Marseille Univ., Institut de Recherche pour le D\u00e9veloppement (IRD) Microbes Evolution Phylogeny and Infections (MEPHI)  27 boulevard Jean Moulin Marseille France"},{"name":"Assistance Publique\u2010H\u00f4pitaux de Marseille (AP\u2010HM)  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00e9my","family":"Delerce","sequence":"additional","affiliation":[{"name":"IHU M\u00e9diterran\u00e9e Infection 19\u201021 boulevard Jean Moulin  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Pontarotti","sequence":"additional","affiliation":[{"name":"IHU M\u00e9diterran\u00e9e Infection 19\u201021 boulevard Jean Moulin  Marseille France"},{"name":"Department of Biological Sciences Centre National de la Recherche 16 Scientifique (CNRS)\u2010SNC5039  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Devaux","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1072 Aix\u2010Marseille Universit\u00e9  Marseille 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