PMC:7074424 / 25252-26330 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7074424","sourcedb":"PMC","sourceid":"7074424","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7074424","text":"Papain-like protease\nThe PLpro cleaves the N-terminal region of the PP to generate three NSPs (NSP 1, 2, and 3).[374] PLpro has a catalytic core domain that contains 316 amino acid, which is responsible for cleaving replicase substrates, and a consensus sequence LXGG was required for cleavage.[78] Higher doses of zinc and zinc conjugates were found to inhibit both types of SARS protease (CLpro and PLpro).[84] Benzodioxole can inhibit the PLpro enzyme. The crystal structure of interaction is shown in PDB ID: 4OVZ, 4OWZ.[31] Through in silico approach, another new lead was identified (6577871) which was further optimized, and compound 15h (S configuration, enzyme IC50 =0.56 μM, antiviral EC50 =9.1 μM) and 15g (R configuration, enzyme IC50 =0.32 μM; antiviral EC50 =9.1 μM) were found to be the most important inhibitors.[32] The crystallized structural details of these interactions can be visualized in the PDB database (PDB ID: 2FE8 and 3E9S).[32]\nMany of the protease inhibitors are being used in the treatment of COVID-19, e.g., lopinavir–ritonavir 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