{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Glaser J"],"funding":["UT-Battelle","Oak Ridge National Laboratory"],"pagination":["255-265"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9003389"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(4)"],"pubmed_abstract":["Inhibition of the SARS-CoV-2 main protease (M<sup>pro</sup>) is a major focus of drug discovery efforts against COVID-19. Here we report a hit expansion of non-covalent inhibitors of M<sup>pro</sup>. Starting from a recently discovered scaffold (The COVID Moonshot Consortium. Open Science Discovery of Oral Non-Covalent SARS-CoV-2 Main Protease Inhibitor Therapeutics. bioRxiv 2020.10.29.339317) represented by an isoquinoline series, we searched a database of over a billion compounds using a cheminformatics molecular fingerprinting approach. We identified and tested 48 compounds in enzyme inhibition assays, of which 21 exhibited inhibitory activity above 50% at 20 μM. Among these, four compounds with IC<sub>50</sub> values around 1 μM were found. Interestingly, despite the large search space"],"journal":["ACS pharmacology & translational science"],"pubmed_title":["Hit Expansion of a Noncovalent SARS-CoV-2 Main Protease Inhibitor."],"pmcid":["PMC9003389"],"funding_grant_id":["DE-AC05-00OR22725","LOIS 10126"],"pubmed_authors":["Kovalevsky A","Parks JM","Smith DMA","Labbe A","Coates L","Del Galdo S","Agarwal R","Sedova A","Davidson RB","Maradzike E","Glaser J","Bykov D","Daidone I","Kneller DW","Hsu DJ","Galanie S","Tharrington A","Smith JC"],"additional_accession":[]},"is_claimable":false,"name":"Hit Expansion of a Noncovalent SARS-CoV-2 Main Protease Inhibitor.","description":"Inhibition of the SARS-CoV-2 main protease (M<sup>pro</sup>) is a major focus of drug discovery efforts against COVID-19. Here we report a hit expansion of non-covalent inhibitors of M<sup>pro</sup>. Starting from a recently discovered scaffold (The COVID Moonshot Consortium. Open Science Discovery of Oral Non-Covalent SARS-CoV-2 Main Protease Inhibitor Therapeutics. bioRxiv 2020.10.29.339317) represented by an isoquinoline series, we searched a database of over a billion compounds using a cheminformatics molecular fingerprinting approach. We identified and tested 48 compounds in enzyme inhibition assays, of which 21 exhibited inhibitory activity above 50% at 20 μM. Among these, four compounds with IC<sub>50</sub> values around 1 μM were found. Interestingly, despite the large search space","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-09T17:37:21.613Z","creation":"2024-11-10T08:43:41.215Z"},"accession":"S-EPMC9003389","cross_references":{"pubmed":["35434531"],"doi":["10.1021/acsptsci.2c00026"]}}