{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:48:22Z","timestamp":1767836902480,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:00:00Z","timestamp":1688947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academic Promotion Program of Shandong First Medical University","award":["2019LJ003"],"award-info":[{"award-number":["2019LJ003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The COVID-19 pandemic has caused severe health threat globally, and novel SARS-Cov-2 inhibitors are urgently needed for antiviral treatment. The main protease (Mpro) of the virus is one of the most effective and conserved targets for anti-SARS-CoV-2 drug development. In this study, we utilized a molecular docking-based virtual screening approach against the conserved catalytic site to identify small-molecule inhibitors of SARS-CoV-2 Mpro. Further biological evaluation helped us identify two compounds, AF-399\/40713777 and AI-942\/42301830, with moderate inhibitory activity. Besides that, the in silico data, including molecular dynamics (MD) simulation, binding free energy calculations, and AMDET profiles, suggested that these two hits could serve as the starting point for the future development of COVID-19 intervention treatments.<\/jats:p>","DOI":"10.3390\/molecules28145320","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T01:58:14Z","timestamp":1689040694000},"page":"5320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["In Silico Discovery of Small-Molecule Inhibitors Targeting SARS-CoV-2 Main Protease"],"prefix":"10.3390","volume":"28","author":[{"given":"Menghan","family":"Gao","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan 250117, China"},{"name":"NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan 250117, China"},{"name":"Key Lab for Rare & Uncommon Diseases of Shandong Province, 6699 Qingdao Road, Jinan 250117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9232-953X","authenticated-orcid":false,"given":"Dongwei","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3274-5416","authenticated-orcid":false,"given":"Na","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-5728","authenticated-orcid":false,"given":"Yanna","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences & Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan 250117, China"},{"name":"NHC Key Laboratory of Biotechnology Drugs, Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan 250117, China"},{"name":"Key Lab for Rare & Uncommon Diseases of Shandong Province, 6699 Qingdao Road, Jinan 250117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/j.cmi.2022.04.018","article-title":"Remdesivir for the treatment of COVID-19: A systematic review and meta-analysis","volume":"28","author":"Lee","year":"2022","journal-title":"Clin. 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