Discovery of Highly Potent Fusion Inhibitors with Potential Pan-Coronavirus Activity That Effectively Inhibit Major COVID-19 Variants of Concern (VOCs) in Pseudovirus-Based Assays.

ABSTRACT: We report the discovery of several highly potent small molecules with low-nM potency against severe acute respiratory syndrome coronavirus (SARS-CoV; lowest half-maximal inhibitory concentration (IC₅₀: 13 nM), SARS-CoV-2 (IC₅₀: 23 nM), and Middle East respiratory syndrome coronavirus (MERS-CoV; IC₅₀: 76 nM) in pseudovirus-based assays with excellent selectivity index (SI) values (>5000), demonstrating potential pan-coronavirus inhibitory activities. Some compounds showed 100% inhibition against the cytopathic effects (CPE; IC₁₀₀) of an authentic SARS-CoV-2 (US_WA-1/2020) variant at 1.25 µM. The most active inhibitors also potently inhibited variants of concern (VOCs), including the UK (B.1.1.7) and South African (B.1.351) variants and the Delta v

SUBMITTER: Curreli F 

PROVIDER: S-EPMC8780828 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature