- Yoshimitsu Kiriyama (Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University / Institute of Neuroscience, Tokushima Bunri University / email@example.com)
1) Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University , 2) Institute of Neuroscience, Tokushima Bunri University
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that caused the global epidemic of COVID-19. 3C-like protease (3CLpro), called the main protease (Mpro), cleaves 11 sites in the long-stranded protein synthesized from viral genomic RNA. After the cleavage of the long-stranded protein, proteins such as RNA-dependent RNA polymerase are cut off and activated. Therefore, 3CLpro is crucial for SARS-CoV-2 replication and is the target of drugs against SARS-CoV-2. Polyphenols and triterpenoids in olives can bind to SARS-CoV-2 3CLpro in in silico and computational studies. However, not all phytochemicals have been shown to inhibit SARS-CoV-2 3CLpro. Here, we examined the inhibitory effects of olive-derived phytochemicals on SARS-CoV-2 3CLpro. Among these phytochemicals, luteolin and oleanolic acid inhibited the 3CLpro activity by about 40%. The actual enzyme inhibitory action of oleanolic acid has not been examined. Thus, we examined the dose response in the inhibition of 3CLpro by oleanolic acid. Oleanolic acid significantly inhibited the enzymatic activity of 3CLpro at concentrations above 50 μM, and it may be a potent molecule that inhibit SARS-CoV-2 replication via 3CLpro inhibition.