{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T08:52:30Z","timestamp":1720947150366},"reference-count":26,"publisher":"Institute of Biochemistry","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BIOMED KHIM"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:p>Docking and quantum-chemical methods have been used for screening of drug-like compounds  from the own database of the Voronezh State University to find inhibitors the SARS-CoV-2 main protease,  an important enzyme of the coronavirus responsible for the COVID-19 pandemic. Using the SOL program more  than 42000 3D molecular structures were docked into the active site of the main protease, and more than 1000 ligands  with most negative values of the SOL score were selected for further processing. For all these top ligands,  the protein-ligand binding enthalpy has been calculated using the PM7 semiempirical quantum-chemical method with  the COSMO implicit solvent model. 20 ligands with the most negative SOL scores and the most negative binding  enthalpies have been selected for further experimental testing. The latter has been made by measurements  of the inhibitory activity against the main protease and suppression of SARS-CoV-2 replication in a cell culture.  The inhibitory activity \\of the compounds was determined using a synthetic fluorescently labeled peptide substrate  including the proteolysis site of the main protease. The antiviral activity was tested against SARS-CoV-2 virus  in the Vero cell culture. Eight compounds showed inhibitory activity against the main protease of SARS-CoV-2  in the submicromolar and micromolar ranges of the IC50 values. Three compounds suppressed coronavirus replication  in the cell culture at the micromolar range of EC50 values and had low cytotoxicity. The found chemically diverse  inhibitors can be used for optimization in order to obtain a leader compound, the basis of new direct-acting antiviral  drugs against the SARS-CoV-2 coronavirus.<\/jats:p>","DOI":"10.18097\/pbmc20216703259","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T16:43:51Z","timestamp":1623948231000},"page":"259-267","source":"Crossref","is-referenced-by-count":2,"title":["Development of antiviral drugs based on inhibitors of the SARS-COV-2 main protease"],"prefix":"10.18097","volume":"67","author":[{"given":"A.V.","family":"Sulimov","sequence":"first","affiliation":[{"name":"Research Computer Center of Lomonosov Moscow State University, Moscow, Russia; Dimonta Ltd., Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kh.S.","family":"Shikhaliev","sequence":"additional","affiliation":[{"name":"Voronezh State University, Voronezh, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.V.","family":"Pyankov","sequence":"additional","affiliation":[{"name":"State Research Centre of Virology and Biotechnology \u201cVector\u201d, Koltsovo, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.N.","family":"Shcherbakov","sequence":"additional","affiliation":[{"name":"State Research Centre of Virology and Biotechnology \u201cVector\u201d, Koltsovo, Russia; Altai State University, Barnaul, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.Yu.","family":"Chirkova","sequence":"additional","affiliation":[{"name":"Altai State University, Barnaul, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.S.","family":"Ilin","sequence":"additional","affiliation":[{"name":"Research Computer Center of Lomonosov Moscow State University, Moscow, Russia; Dimonta Ltd., Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.C.","family":"Kutov","sequence":"additional","affiliation":[{"name":"Research Computer Center of Lomonosov Moscow State University, Moscow, Russia; Dimonta Ltd., Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.S.","family":"Tashchilova","sequence":"additional","affiliation":[{"name":"Research Computer Center of Lomonosov Moscow State University, Moscow, Russia; Dimonta Ltd., Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.Yu.","family":"Krysin","sequence":"additional","affiliation":[{"name":"Voronezh State University, Voronezh, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.V.","family":"Krylskiy","sequence":"additional","affiliation":[{"name":"Voronezh State University, Voronezh, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.V.","family":"Stolpovskaya","sequence":"additional","affiliation":[{"name":"Voronezh State University, Voronezh, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.A.","family":"Volosnikova","sequence":"additional","affiliation":[{"name":"State Research Centre of Virology and Biotechnology \u201cVector\u201d, Koltsovo, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.V.","family":"Belenkaya","sequence":"additional","affiliation":[{"name":"State Research Centre of Virology and Biotechnology \u201cVector\u201d, Koltsovo, Russia; Novosibirsk State University, Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.B.","family":"Sulimov","sequence":"additional","affiliation":[{"name":"Research Computer Center of Lomonosov Moscow State University, Moscow, Russia; Dimonta Ltd., Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7443","published-online":{"date-parts":[[2021]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W., Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L.Y.-Z., Dai F.-H., Liu Y., Wang Q.-M., Zheng J.-J., Xu L., Holmes E.C., Zhang Y.-L.Y.-Z. 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