Natural products for targeting SARS-CoV-2 enzymes, RNA-dependent RNA polymerase and main protease

Abstract

Natural products have consistently played a crucial role in human disease treatment, accounting for approximately 80% of current marketed drugs. The recent global COVID-19 pandemic has led to increased interest in plant-derived compounds as potential antiviral agents. This review summarizes the potential of natural compounds targeting SARS-CoV-2 enzymes, specifically against RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). Additionally, this review focused on secondary metabolites from various plant or foodbased sources, such as flavonoids, polyphenols, and isothiocyanates. Although numerous natural products have been found to show inhibitory activity against RdRp and Mpro, only the natural products that have moderate to high inhibitory activity were included in this study. Compounds like baicalein, myricetin, and curcumin have demonstrated efficacy in vitro; however, their clinical application is hindered by challenges related to bioavailability and potency. Strategies to enhance the antiviral potential of these compounds include structural modification, nanotechnology, and combination therapy. Also, development of synthesis method for these compounds is crucial for commercializing. This review provides an overview of key natural inhibitors of SARS-CoV-2 enzymes, Mpro or RdRp, emphasizing their promise and addressing the remaining challenges in developing effective natural product-based antiviral therapies.