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The 3C-Like proteinase (3CL<jats:sup>pro<\/jats:sup>) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as an important drug target due to its role in viral replication. The lack of a potent 3CL<jats:sup>pro<\/jats:sup>inhibitor and the availability of the X-ray crystal structure of 3CL<jats:sup>pro<\/jats:sup>(PDB-ID 6LU7) motivated us to perform computational studies to identify commercially available potential inhibitors. A combination of modeling studies was performed to identify potential 3CL<jats:sup>pro<\/jats:sup>inhibitors from the protease inhibitor database MEROPS (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.ebi.ac.uk\/merops\/index.shtml\">https:\/\/www.ebi.ac.uk\/merops\/index.shtml<\/jats:ext-link>). Binding energy evaluation identified key residues for inhibitor design. We found 15 potential 3CL<jats:sup>pro<\/jats:sup>inhibitors with higher binding affinity than that of an \u03b1-ketoamide inhibitor determined via X-ray structure. Among them, saquinavir and three other investigational drugs aclarubicin, TMC-310911, and faldaprevir could be suggested as potential 3CL<jats:sup>pro<\/jats:sup>inhibitors. We recommend further experimental investigation of these compounds.<\/jats:p>","DOI":"10.1038\/s41598-020-74468-0","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T10:14:55Z","timestamp":1603102495000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":131,"title":["Rational approach toward COVID-19 main protease inhibitors via molecular docking, molecular dynamics simulation and free energy calculation"],"prefix":"10.1038","volume":"10","author":[{"given":"Seketoulie","family":"Keretsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swapnil P.","family":"Bhujbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Joo","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,19]]},"reference":[{"key":"74468_CR1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.46234\/ccdcw2020.032","volume":"2","author":"V Surveillances","year":"2020","unstructured":"Surveillances, V. 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