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Recently, vaccines from various companies have been urgently approved to control SARS\u2010CoV\u20102 infections. However, any specific antiviral drug has not been confirmed so far for regular treatment. An important target is the main protease (M\n                    <jats:sup>pro<\/jats:sup>\n                    ), which plays a major role in replication of the virus. In this study, Gaussian and residue network models are employed to reveal two distinct potential allosteric sites on M\n                    <jats:sup>pro<\/jats:sup>\n                    that can be evaluated as drug targets besides the active site. Then, Food and Drug Administration (FDA)\u2010approved drugs are docked to three distinct sites with flexible docking using AutoDock Vina to identify potential drug candidates. Fourteen best molecule hits for the active site of M\n                    <jats:sup>pro<\/jats:sup>\n                    are determined. Six of these also exhibit high docking scores for the potential allosteric regions. Full\u2010atom molecular dynamics simulations with MM\u2010GBSA method indicate that compounds docked to active and potential allosteric sites form stable interactions with high binding free energy (\u2206\n                    <jats:italic>G<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>bind<\/jats:italic>\n                    <\/jats:sub>\n                    ) values. \u2206\n                    <jats:italic>G<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>bind<\/jats:italic>\n                    <\/jats:sub>\n                    values reach \u221252.06\u00a0kcal\/mol for the active site, \u221251.08\u00a0kcal\/mol for the potential allosteric site 1, and\u2009\u2212\u200942.93\u00a0kcal\/mol for the potential allosteric site 2. Energy decomposition calculations per residue elucidate key binding residues stabilizing the ligands that can further serve to design pharmacophores. This systematic and efficient computational analysis successfully determines ivermectine, diosmin, and selinexor currently subjected to clinical trials, and further proposes bromocriptine, elbasvir as M\n                    <jats:sup>pro<\/jats:sup>\n                    inhibitor candidates to be evaluated against SARS\u2010CoV\u20102 infections.\n                  <\/jats:p>","DOI":"10.1002\/prot.26164","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T23:03:07Z","timestamp":1624575787000},"page":"1425-1441","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Repurposing of\n                    <scp>FDA<\/scp>\n                    \u2010approved drugs against active site and potential allosteric drug\u2010binding sites of\n                    <scp>COVID<\/scp>\n                    \u201019 main protease"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3257-1097","authenticated-orcid":false,"given":"Merve","family":"Yuce","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering Istanbul Technical University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9391-7496","authenticated-orcid":false,"given":"Erdem","family":"Cicek","sequence":"additional","affiliation":[{"name":"Computational Science and Engineering Division Informatics Institute, Istanbul Technical University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4762-713X","authenticated-orcid":false,"given":"Tugce","family":"Inan","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Istanbul Technical University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aslihan Basak","family":"Dag","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Istanbul Technical University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0228-3211","authenticated-orcid":false,"given":"Ozge","family":"Kurkcuoglu","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Istanbul Technical University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3245-742X","authenticated-orcid":false,"given":"Fethiye Aylin","family":"Sungur","sequence":"additional","affiliation":[{"name":"Computational Science and Engineering Division Informatics Institute, Istanbul Technical University  Istanbul 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