molecules of the month

S-217622 is the first oral, non-covalent, non-peptidic SARS-CoV-2 3CL (main protease) inhibitor clinical candidate, currently in Ph. II/III trials as a once-daily oral treatment for COVID-19. Unlike paxlovid, the molecule is a non-covalent inhibitor, which may lead to a better safety profile in large populations, though there is no reason to expect issues with reversible covalent paxlovid today. Paxlovid is also the combination of the peptidic drug PF-07321332 with a PK booster, ritonavir, and a single drug with sufficient PK for standalone oral dosing would be ideal for broadest adoption. The starting point was identified by virtual screening, with the top 300 hits being confirmed by high-throughput mass spectrometry. The starting point was weakly biochemically active (3CLpro IC50 of 8.6…