{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:11:49Z","timestamp":1793106709643,"version":"4.5.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFC2309100"],"award-info":[{"award-number":["2023YFC2309100"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["92269118, 92269205, 92369117"],"award-info":[{"award-number":["92269118, 92269205, 92369117"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Scientific Rsearch Project of Jiangsu Health Comission","award":["M2022013"],"award-info":[{"award-number":["M2022013"]}]},{"name":"Project of Chinese Hospital Reform and Development Institute","award":["NDYG2022003"],"award-info":[{"award-number":["NDYG2022003"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,4,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Simnotrelvir is an oral small-molecule antiviral agent targeting the 3C-like protease (3CL\n              <jats:sup>pro<\/jats:sup>\n              ) of SARS-CoV-2, proven effective against the Delta variant with favorable pharmacokinetics and safety in preclinical study. In this study, we further evaluated the antiviral efficacy of simnotrelvir against a range of emerging Omicron variants, including BA.1, BA.4, BA.5, CH.1.1, XBB.1.5, XBB.1.16, EG.5, and JN.1.\n              <jats:italic>In vitro<\/jats:italic>\n              assays with Vero E6 cells confirmed that simnotrelvir exhibited robust antiviral activity across these variants, comparable to the Food and Drug Administration (FDA)-approved drug nirmatrelvir. Additionally, simnotrelvir demonstrated effective inhibition against several nirmatrelvir-resistant SARS-CoV-2 3CL\n              <jats:sup>pro<\/jats:sup>\n              mutants, including A260V, Y54A, (T21I + S144A), F140A, H172Y, and E166V. Importantly, simnotrelvir showed better potency against the E166V mutation compared to nirmatrelvir. Resistance selection studies revealed that BA.5 developed reduced sensitivity after 5 and 10 passages, increasing the IC\n              <jats:sub>50<\/jats:sub>\n              values by 3.2 and 4.5-fold, respectively, while HCoV-OC43 showed an 8.3-fold increase after 12 passages. Despite this, simnotrelvir\u2019s overall efficacy remains strong. Furthermore, clinical trials demonstrated that combining simnotrelvir with ritonavir significantly shortened symptom resolution in COVID-19 patients. Genomic analysis of treated patients found random nucleotide substitutions but no significant mutations linked to 3CL\n              <jats:sup>pro<\/jats:sup>\n              resistance. In conclusion, simnotrelvir shows strong antiviral activity against SARS-CoV-2 variants and maintains a high barrier to resistance, reinforcing its potential as an effective therapeutic option for current and future SARS-CoV-2 variants.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01556-24","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T14:02:28Z","timestamp":1741615348000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Potent antiviral activity of simnotrelvir against key epidemic SARS-CoV-2 variants with a high resistance barrier"],"prefix":"10.1128","volume":"69","author":[{"given":"Liwei","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3656-2187","authenticated-orcid":false,"given":"Chuang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Simcere Pharmaceutical Company Limited","place":["Nanjing, China"]},{"name":"State Key Laboratory of Neurology and Oncology Drug Development","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Simcere Pharmaceutical Company Limited","place":["Nanjing, China"]},{"name":"State Key Laboratory of Neurology and Oncology Drug Development","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Simcere Zaiming Pharmaceutical Company Limited","place":["Shanghai, China"]},{"name":"Department of Chemical Engineering, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Simcere Pharmaceutical Company Limited","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hubei Provincial Center for Disease Control and Prevention","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Pan","sequence":"additional","affiliation":[{"name":"Hubei Provincial Center for Disease Control and Prevention","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoi-Yan","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection,The University of Hong Kong","place":["Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan Fan-Ngai","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection,The University of Hong Kong","place":["Hong Kong SAR, China"]},{"name":"Department of Medicine, Queen Mary Hospital, The University of Hong Kong","place":["Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok-Hung","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection,The University of Hong Kong","place":["Hong Kong SAR, China"]},{"name":"Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park","place":["Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Simcere Pharmaceutical Company Limited","place":["Nanjing, China"]},{"name":"State Key Laboratory of Neurology and Oncology Drug Development","place":["Nanjing, 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