In silico analysis of dietary polyphenols and their gut microbial metabolites suggest inhibition of SARS-CoV-2 infection, replication, and host inflammatory mediators.

ABSTRACT

The outcome of SARS-CoV-2 infection ranges from asymptomatic to severe COVID-19 and death resulting from an exaggerated immune response termed cytokine storm. Epidemiological data have associated consumption of a high-quality plant-based diet with decreased incidence and severity of COVID-19. Dietary polyphenols and their microbial metabolites (MMs) have anti-viral and anti-inflammatory activities. Autodock Vina and Yasara were used in molecular docking and dynamics studies to investigate potential interactions of 7 parent polyphenols (PPs) and 11 MMs with the α- and Omicron variants of the SARS-CoV-2 spike glycoprotein (SGP), papain-like pro-tease (PLpro) and 3 chymotrypsin-like protease (3CLpro), as well as host inflammatory mediators including complement component 5a (C5a), C5a receptor (C5aR), and C-C chemokine receptor type 5 (CCR5). PPs and MMs interacted to varying degrees with residues on target viral and host inflammatory proteins showing potential as competitive inhibitors. Based on these in silico findings, PPs and MMs may inhibit SARS-CoV-2 infection, replication, and/or modulate host immunity in the gut or periphery. Such inhibition may explain why people that consume a high-quality plant-based diet have less incidence and severity of COVID-19.Communicated by Ramaswamy H. Sarma.