{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:44:16Z","timestamp":1775522656851,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T00:00:00Z","timestamp":1650672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["20-51-55001"],"award-info":[{"award-number":["20-51-55001"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Foundation of China","award":["82161138005"],"award-info":[{"award-number":["82161138005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2\u2032-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein\u2013ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing.<\/jats:p>","DOI":"10.3390\/molecules27092721","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T21:39:45Z","timestamp":1650749985000},"page":"2721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel Inhibitors of 2\u2032-O-Methyltransferase of the SARS-CoV-2 Coronavirus"],"prefix":"10.3390","volume":"27","author":[{"given":"Alexey","family":"Sulimov","sequence":"first","affiliation":[{"name":"Research Computing Center, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-6522","authenticated-orcid":false,"given":"Danil","family":"Kutov","sequence":"additional","affiliation":[{"name":"Research Computing Center, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Ilin","sequence":"additional","affiliation":[{"name":"Research Computing Center, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yibei","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Sulimov","sequence":"additional","affiliation":[{"name":"Research Computing Center, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1056\/NEJMoa030781","article-title":"A novel coronavirus associated with severe acute respiratory syndrome","volume":"348","author":"Ksiazek","year":"2003","journal-title":"N. 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