2. Academic Validation
  3. Systematic Studies on the Anti-SARS-CoV-2 Mechanisms of Tea Polyphenol-Related Natural Products

Systematic Studies on the Anti-SARS-CoV-2 Mechanisms of Tea Polyphenol-Related Natural Products

  • ACS Omega. 2024 May 17;9(22):23984-23997. doi: 10.1021/acsomega.4c02392.
Chen-Wei Li 1,  Tai-Ling Chao 2,  Chin-Lan Lai 1,  Cheng-Chin Lin 1,  Max Yu-Chen Pan 3,  Chieh-Ling Cheng 1,  Chih-Jung Kuo 4,  Lily Hui-Ching Wang 3,  Sui-Yuan Chang 2 5,  Po-Huang Liang 6 1
Affiliations

Affiliations

  • 1 Institute of Biochemical Sciences, National Taiwan University, Taipei 10617, Taiwan.
  • 2 Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 10048, Taiwan.
  • 3 Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
  • 4 Department of Veterinary Medicine, National Chung Hsing University, Taichung 40227, Taiwan.
  • 5 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
  • 6 Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
PMID: 38854515 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 (3CLpro) and papain-like protease (PLpro) 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.

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