Systematic Studies on the Anti-SARS-CoV-2 Mechanisms of Tea Polyphenol-Related Natural Products
Journal
ACS omega
Journal Volume
9
Journal Issue
22
Start Page
23984
End Page
23997
ISSN
2470-1343
Date Issued
2024-06-04
Author(s)
Li, Chen-Wei
Lai, Chin-Lan
Lin, Cheng-Chin
Pan, Max Yu-Chen
Cheng, Chieh-Ling
Kuo, Chih-Jung
Wang, Lily Hui-Ching
Liang, Po-Huang
DOI
10.1021/acsomega.4c02392
Abstract
The causative pathogen of COVID-19, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), utilizes the receptor-binding domain (RBD) of the spike protein to bind to human receptor angiotensin-converting enzyme 2 (ACE2). Further cleavage of spike by human proteases furin, TMPRSS2, and/or cathepsin L facilitates viral entry into the host cells for replication, where the maturation of polyproteins by 3C-like protease (3CL) and papain-like protease (PL) yields functional nonstructural proteins (NSPs) such as RNA-dependent RNA polymerase (RdRp) to synthesize mRNA of structural proteins. By testing the tea polyphenol-related natural products through various assays, we found that the active antivirals prevented SARS-CoV-2 entry by blocking the RBD/ACE2 interaction and inhibiting the relevant human proteases, although some also inhibited the viral enzymes essential for replication. Due to their multitargeting properties, these compounds were often misinterpreted for their antiviral mechanisms. In this study, we provide a systematic protocol to check and clarify their anti-SARS-CoV-2 mechanisms, which should be applicable for all of the antivirals.
Type
journal article