Discovery of Highly Potent Small Molecule Pan-Coronavirus Fusion Inhibitors.

ABSTRACT: The unprecedented pandemic of COVID-19, caused by a novel coronavirus, SARS-CoV-2, and its highly transmissible variants, led to massive human suffering, death, and economic devastation worldwide. Recently, antibody-evasive SARS-CoV-2 subvariants, BQ and XBB, have been reported. Therefore, the continued development of novel drugs with pan-coronavirus inhibition is critical to treat and prevent infection of COVID-19 and any new pandemics that may emerge. We report the discovery of several highly potent small-molecule inhibitors. One of which, NBCoV63, showed low nM potency against SARS-CoV-2 (IC₅₀: 55 nM), SARS-CoV-1 (IC₅₀: 59 nM), and MERS-CoV (IC₅₀: 75 nM) in pseudovirus-based assays with excellent selectivity indices (SI > 900), suggesting its pan-coronav

SUBMITTER: Curreli F 

PROVIDER: S-EPMC10141620 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature