Sulfoquinovosyl diacylglycerol, a component of Holy Basil Ocimum tenuiflorum, inhibits the activity of the SARS-CoV-2 main protease and viral replication in vitro.

The persistence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of new mutant strains continue to present a substantial threat with potential for future pandemics. Safe, effective, and readily available COVID-19 therapeutics are urgently needed to prepare for future coronavirus pandemics. To help identify new antiviral agents, the present study focused on natural products in the extracts of Holy Basil, Ocimum tenuiflorum L., which show potential inhibitory effects against the SARS-CoV-2 main protease (M(pro)). Bioassay-guided isolation of the MeOH extracts of O. tenuiflorum led to the identification of a sulfur-containing glyceroglycolipid, sulfoquinovosyl diacylglycerol (SQDG: 1), as a potent M(pro) inhibitor that effectively inhibited M(pro) activity (IC(50): 0.42 µM). SQDG (1) also markedly suppressed SARS-CoV-2 replication (EC(50), 51.2 µM) in vitro while displaying no cytotoxicity (CC(50) > 100 µM). Further inhibition kinetic studies and docking simulations clearly demonstrated that SQDG strongly inhibited SARS-CoV-2 M(pro) in a competitive and mixed-inhibition manner. These findings highlight SQDG as a promising lead compound for COVID-19 therapy and emphasize the need to explore new drugs from natural sources.