Onnamide A suppresses the severe acute respiratory syndrome-coronavirus 2 infection without inhibiting 3-chymotrypsin-like cysteine protease.

This article focuses on the identification and characterization of onnamide A, a compound isolated from the marine sponge Theonella swinhoei collected in Okinawa, Japan, as a potential antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Onnamide A demonstrated inhibitory activity against multiple SARS-CoV-2 variants, including Alpha, Delta, and Omicron, by reducing virus-induced cytopathic effects and viral production in cell culture, with partial suppression of viral entry independent of TMPRSS2 enzymatic activity. Although molecular docking suggested possible inhibition of the viral 3-chymotrypsin-like cysteine protease (3CLpro), in vitro assays showed no direct effect of onnamide A on 3CLpro activity. The study highlights onnamide A as a promising lead compound for anti-SARS-CoV-2 drug development, while noting that its precise antiviral mechanism and cytotoxicity require further investigation.