Multidose evaluation of 6,710 drug repurposing library identifies potent SARS-CoV-2 infection inhibitors In Vitro and In Vivo.

A bioinformatically rich library of pharmacologically active small molecules with diverse chemical scaffolds and including known host targets were used to identify hundreds of SARS-CoV-2 replication inhibitors using in vitro, ex vivo, and in vivo models. Extending our previous work, unbiased screening demonstrated a propensity for compounds targeting host proteins that interact with virus proteins. Representatives from multiple chemical classes revealed differences in cell susceptibility, suggesting distinct dependencies on host factors and one, Obatoclax, showed 90% reduction of lung virus loads in the mouse disease model. Our findings and integrated analytical approaches will have important implications for future drug screening and how therapies are developed against SARS-CoV-2 and other viruses.