Discovery of chebulagic acid and punicalagin as novel allosteric inhibitors of SARS-CoV-2 3CLpro

  • Antiviral Res. 2021 Jun;190:105075. doi: 10.1016/j.antiviral.2021.105075.
Ruikun Du  1 ,  Laura Cooper  2 ,  Zinuo Chen  3 ,  Hyun Lee  4 ,  Lijun Rong  5 ,  Qinghua Cui  6
Affiliations
  • 1. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266122, China.
  • 2. Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA.
  • 3. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
  • 4. Department of Pharmaceutical Sciences, Center for Biomolecular Sciences, College of Pharmacy, Biophysics Core at Research Resources Center, University of Illinois at Chicago, Chicago, IL, 60607, USA.
  • 5. Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA. Electronic address: [email protected].
  • 6. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China; Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266122, China. Electronic address: [email protected].
PMID: 33872675 DOI: 10.1016/j.antiviral.2021.105075
Abstract

The emerging SARS-CoV-2 Infection is the cause of the global COVID-19 pandemic. To date, there are limited therapeutic options available to fight this disease. Here we examined the inhibitory abilities of two broad-spectrum Antiviral natural products chebulagic acid (CHLA) and punicalagin (PUG) against SARS-CoV-2 viral replication. Both CHLA and PUG reduced virus-induced plaque formation in Vero-E6 monolayer at noncytotoxic concentrations, by targeting the enzymatic activity of viral 3-chymotrypsin-like cysteine protease (3CLpro) as allosteric regulators. Our study demonstrates the potential use of CHLA and PUG as novel COVID-19 therapies.

Keywords
3CLpro; Allosteric inhibitor; Chebulagic acid; Punicalagin; SARS-CoV-2.
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