{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:27:01Z","timestamp":1790670421636,"version":"4.1.0"},"reference-count":62,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"30","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,7,26]]},"abstract":"<jats:p>\n                    To facilitate the detection and management of potential clinical antiviral resistance, in vitro selection of drug-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) against the virus M\n                    <jats:sup>pro<\/jats:sup>\n                    inhibitor nirmatrelvir (Paxlovid active component) was conducted. Six M\n                    <jats:sup>pro<\/jats:sup>\n                    mutation patterns containing T304I alone or in combination with T21I, L50F, T135I, S144A, or A173V emerged, with A173V+T304I and T21I+S144A+T304I mutations showing &gt;20-fold resistance each. Biochemical analyses indicated inhibition constant shifts aligned to antiviral results, with S144A and A173V each markedly reducing nirmatrelvir inhibition and M\n                    <jats:sup>pro<\/jats:sup>\n                    activity. SARS-CoV-2 surveillance revealed that in vitro resistance\u2013associated mutations from our studies and those reported in the literature were rarely detected in the Global Initiative on Sharing All Influenza Data database. In the Paxlovid Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients trial, E166V was the only emergent resistance mutation, observed in three Paxlovid-treated patients, none of whom experienced COVID-19\u2013related hospitalization or death.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adl4013","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T13:59:07Z","timestamp":1721829547000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":59,"title":["In vitro selection and analysis of SARS-CoV-2 nirmatrelvir resistance mutations contributing to clinical virus resistance surveillance"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9831-6836","authenticated-orcid":true,"given":"Yuao","family":"Zhu","sequence":"first","affiliation":[{"name":"Pfizer Worldwide Research, Development &amp; Medical, Pearl River, NY 10965, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2081-7907","authenticated-orcid":true,"given":"Irina","family":"Yurgelonis","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development &amp; 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