PMC:7600245 / 65566-66788 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7600245","sourcedb":"PMC","sourceid":"7600245","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7600245","text":"It an orally bioavailable, small molecule, reversible covalent inhibitor of calpains, non-lysosomal cysteine proteases, with anti-fibrotic activity. BLD-2660 exhibited potent and selective inhibition of calpains 1,2, and 9 and thus was found to be efficacious in multiple animal fibrosis models of skin, liver, and lung. It exhibited high selectivity against related cysteine proteases. Earlier, several calpain inhibitors were found to reduce the viral replication of SARS-CoV-1 [232,233]. The antiviral activity by calpain inhibition was also verified using siRNA to selectively silence expression of the calpain 2 isoform in SARS-CoV infected cells [232,233]. Undisclosed inhibitors by the developing company were found to reduce SARS-CoV-2 replication in Vero cell-based assays. Furthermore, in preclinical animal models of lung injury and fibrosis, BLD-2660 was shown to reduce the expression/production of IL-6 in injured lungs and to reduce fibrosis [234]. Owing to the antiviral and anti-inflammatory activities of BLD-2660, it has been advanced to a phase 2, randomized, double-blind, placebo-controlled study to evaluate its safety and antiviral activity in COVID-19 hospitalized subjects (NCT04334460; n = 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