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 (PL^pro) and 3 chymotrypsin-like protease (3CL^pro), 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

Keywords:

• SARS-CoV-2
• coronavirus
• inflammation
• complement
• cytokine storm
• dietary polyphenols
• microbial metabolites

Author contributions

DER and EM planned the study. EM and HH performed docking and dynamics studies, analyzed results, created tables and figures. SS created figures and drafted results sections. EM drafted the manuscript and DER wrote the final manuscript. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

EM, HH, and SS have no competing interests. DER has equity in Nutrasorb LLC.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

We thank NIH/NCCIH R01AT010242 for research support.