{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dampalla CS"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","HHS | NIH | National Institute of Allergy and Infectious Diseases","NIGMS NIH HHS"],"pagination":["e2101555118"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8307543"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["118(29)"],"pubmed_abstract":["Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a serious global public health threat. The 3C-like protease (3CLpro) is a virus protease encoded by SARS-CoV-2, which is essential for virus replication. We have previously reported a series of small-molecule 3CLpro inhibitors effective for inhibiting replication of human coronaviruses including SARS-CoV-2 in cell culture and in animal models. Here we generated a series of deuterated variants of a 3CLpro inhibitor, GC376, and evaluated the antiviral effect against SARS-CoV-2. The deuterated GC376 displayed potent inhibitory activity against SARS-CoV-2 in the enzyme- and the cell-based assays. The K18-hACE2 mice develop mild to lethal infection commensurate with SARS-CoV-2 challenge doses and were propose"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Postinfection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection."],"pmcid":["PMC8307543"],"funding_grant_id":["R01 AI129269","P30 DK054759","R01 AI109039","P30 GM133893","T32 AI007511","P01 AI060699"],"pubmed_authors":["Meyerholz DK","Perlman S","Groutas WC","Nguyen HN","Perera KD","Lovell S","Dampalla CS","Wong LR","Zheng J","Kashipathy MM","Chang KO","Kim Y","Battaile KP"],"additional_accession":[]},"is_claimable":false,"name":"Postinfection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection.","description":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a serious global public health threat. The 3C-like protease (3CLpro) is a virus protease encoded by SARS-CoV-2, which is essential for virus replication. We have previously reported a series of small-molecule 3CLpro inhibitors effective for inhibiting replication of human coronaviruses including SARS-CoV-2 in cell culture and in animal models. Here we generated a series of deuterated variants of a 3CLpro inhibitor, GC376, and evaluated the antiviral effect against SARS-CoV-2. The deuterated GC376 displayed potent inhibitory activity against SARS-CoV-2 in the enzyme- and the cell-based assays. The K18-hACE2 mice develop mild to lethal infection commensurate with SARS-CoV-2 challenge doses and were propose","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jul","modification":"2026-05-08T05:35:12.904Z","creation":"2022-02-11T00:13:33.22Z"},"accession":"S-EPMC8307543","cross_references":{"pubmed":["34210738"],"doi":["10.1073/pnas.2101555118"]}}