{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:35:35Z","timestamp":1790789735735,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFF1204900"],"award-info":[{"award-number":["2023YFF1204900"]}]},{"name":"National Key Research and Development Program of China","award":["2023YFF1204902"],"award-info":[{"award-number":["2023YFF1204902"]}]},{"name":"National Key Research and Development Program of China","award":["2023A0505010015"],"award-info":[{"award-number":["2023A0505010015"]}]},{"name":"Guangdong-Hong Kong Technology Cooperation Funding Scheme","award":["2023YFF1204900"],"award-info":[{"award-number":["2023YFF1204900"]}]},{"name":"Guangdong-Hong Kong Technology Cooperation Funding Scheme","award":["2023YFF1204902"],"award-info":[{"award-number":["2023YFF1204902"]}]},{"name":"Guangdong-Hong Kong Technology Cooperation Funding Scheme","award":["2023A0505010015"],"award-info":[{"award-number":["2023A0505010015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The ongoing COVID-19 pandemic still threatens human health around the world. The methyltransferases (MTases) of SARS-CoV-2, specifically nsp14 and nsp16, play crucial roles in the methylation of the N7 and 2\u2032-O positions of viral RNA, making them promising targets for the development of antiviral drugs. In this work, we performed structure-based virtual screening for nsp14 and nsp16 using the screening workflow (HTVS, SP, XP) of Schr\u00f6dinger 2019 software, and we carried out biochemical assays and molecular dynamics simulation for the identification of potential MTase inhibitors. For nsp14, we screened 239,000 molecules, leading to the identification of three hits A1\u2013A3 showing N7-MTase inhibition rates greater than 60% under a concentration of 50 \u00b5M. For the SAM binding and nsp10-16 interface sites of nsp16, the screening of 210,000 and 237,000 molecules, respectively, from ZINC15 led to the discovery of three hit compounds B1\u2013B3 exhibiting more than 45% of 2\u2032-O-MTase inhibition under 50 \u00b5M. These six compounds with moderate MTase inhibitory activities could be used as novel candidates for the further development of anti-SARS-CoV-2 drugs.<\/jats:p>","DOI":"10.3390\/molecules29102312","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T03:35:55Z","timestamp":1715744155000},"page":"2312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structure-Based Virtual Screening for Methyltransferase Inhibitors of SARS-CoV-2 nsp14 and nsp16"],"prefix":"10.3390","volume":"29","author":[{"given":"Kejue","family":"Wu","sequence":"first","affiliation":[{"name":"Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinfeng","family":"Guo","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiefeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-Sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9335-3877","authenticated-orcid":false,"given":"Weifeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyin","family":"Guo","sequence":"additional","affiliation":[{"name":"Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-Sen University, Shenzhen 518107, China"},{"name":"Guangzhou Laboratory, Bio-Island, Guangzhou 510320, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Cao","sequence":"additional","affiliation":[{"name":"Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-Sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinping","family":"Lei","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1007\/s11030-021-10211-9","article-title":"Identification of potential plant-based inhibitor against viral proteases of SARS-CoV-2 through molecular docking, mm-pbsa binding energy calculations and molecular dynamics simulation","volume":"25","author":"Gogoi","year":"2021","journal-title":"Mol. 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