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Jun12197 for COVID-19

Jun12197 has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Tan et al., Design of SARS-CoV-2 papain-like protease inhibitor with antiviral efficacy in a mouse model, bioRxiv, doi:10.1101/2023.12.01.569653
AbstractThe emergence of SARS-CoV-2 variants and drug-resistant mutants calls for additional oral antivirals. The SARS-CoV-2 papain-like protease (PLpro) is a promising but challenging drug target. In this study, we designed and synthesized 85 noncovalent PLproinhibitors that bind to the newly discovered Val70Ubsite and the known BL2 groove pocket. Potent compounds inhibited PLprowith inhibitory constant Kivalues from 13.2 to 88.2 nM. The co-crystal structures of PLprowith eight leads revealed their interaction modes. Thein vivoleadJun12682inhibited SARS-CoV-2 and its variants, including nirmatrelvir-resistant strains with EC50from 0.44 to 2.02 ┬ÁM. Oral treatment withJun12682significantly improved survival and reduced lung viral loads and lesions in a SARS-CoV-2 infection mouse model, suggesting PLproinhibitors are promising oral SARS-CoV-2 antiviral candidates.One-Sentence SummaryStructure-guided design of SARS-CoV-2 PLproinhibitors within vivoantiviral efficacy in a mouse model.
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