{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:29:36Z","timestamp":1770337776329,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,11]],"date-time":"2021-09-11T00:00:00Z","timestamp":1631318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K08257"],"award-info":[{"award-number":["17K08257"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19J23595"],"award-info":[{"award-number":["19J23595"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K15244"],"award-info":[{"award-number":["21K15244"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["20H05883"],"award-info":[{"award-number":["20H05883"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recently, inhibitors of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) have been proposed as potential therapeutic agents for COVID-19. Studying effects of amino acid mutations in the conformation of drug targets is necessary for anticipating drug resistance. In this study, with the structure of the SARS-CoV-2 Mpro complexed with a non-covalent inhibitor, we performed molecular dynamics (MD) simulations to determine the conformation of the complex when single amino acid residue in the active site is mutated. As a model of amino acid mutation, we constructed mutant proteins with one residue in the active site mutated to alanine. This method is called virtual alanine scan. The results of the MD simulations showed that the conformation and configuration of the ligand was changed for mutants H163A and E166A, although the structure of the whole protein and of the catalytic dyad did not change significantly, suggesting that mutations in His163 and Glu166 may be linked to drug resistance.<\/jats:p>","DOI":"10.3390\/ijms22189837","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T21:45:57Z","timestamp":1631483157000},"page":"9837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Virtual Alanine Scan of the Main Protease Active Site in Severe Acute Respiratory Syndrome Coronavirus 2"],"prefix":"10.3390","volume":"22","author":[{"given":"Tomoki","family":"Nakayoshi","sequence":"first","affiliation":[{"name":"Graduate School of Information Sciences, Hiroshima City University, 3-4-1 Ozukahigashi, Asaminami-ku, Hiroshima 731-3194, Hiroshima, Japan"},{"name":"Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Kato","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Aichi, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, 16-48 Kamishinano, Totsuka-ku, Yokohama 244-0806, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Kurimoto","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akifumi","family":"Oda","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Aichi, Japan"},{"name":"Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita 565-0871, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/cmdc.202000223","article-title":"Drug development and medicinal chemistry efforts toward SARS-coronavirus and Covid-19 therapeutics","volume":"15","author":"Ghosh","year":"2020","journal-title":"ChemMedChem"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jhep.2020.09.031","article-title":"COVID-19: Discovery, diagnostics and drug development","volume":"74","author":"Asselah","year":"2021","journal-title":"J. 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