SARS-CoV-2 Main Protease Inhibitors from Natural Product Repository as Therapeutic Candidates for the Treatment of Coronaviridae Infections.

BACKGROUND:The main protease (Mpro) is a crucial enzyme for the life cycle of SARS-CoV-2 and a validated target for the treatment of COVID-19 infection. Natural products have been a proper alternative for treating viral diseases by modulating different steps of the life cycle of many viruses. OBJECTIVE:This review article is designed to summarize the cumulative information of natural-derived Mpro inhibitors that are validated by experimental biological testing. METHODS:The natural-derived Mpro inhibitors of SARS-CoV-2 that have been discovered since the emergence of the COVID-19 pandemic are reviewed in this article. Only natural products with experimental validation are reported in this article. Collected compounds are classified according to their chemical identity into flavonoids, phenolic acids, quinones, alkaloids, chromones, stilbenes, tannins, lignans, terpenes, and other polyphenolic and miscellaneous natural-derived Mpro inhibitors. CONCLUSION:These compounds could serve as scaffolds for further lead-structure optimization for desirable potency, a larger margin of safety, and better oral activity.