Punicalagin and zinc (II) ions inhibit the activity of SARS-CoV-2 3CL-protease in vitro

Eur Rev Med Pharmacol Sci. 2021 May;25(10):3908-3913. doi: 10.26355/eurrev_202105_25958.

Abstract

Objective: Coronavirus 2019 (COVID-19) has now been declared as a worldwide pandemic. Currently, no drugs have been endorsed for its treatment; in this manner, a pressing need has been developed for any antiviral drugs that will treat COVID-19. Coronaviruses require the SARS-CoV-2 3CL-Protease (3CL-protease) for cleavage of its polyprotein to yield a single useful protein and assume a basic role in the disease progression. In this study, we demonstrated that punicalagin, the fundamental active element of pomegranate in addition to the combination of punicalagin with zinc (Zn) II, appear to show powerful inhibitory activity against SARS-CoV-2.

Materials and methods: The 3CL protease assay kit was used to quantify 3CL protease action. The tetrazolium dye, MTS, was used to evaluate cytotoxicity.

Results: Punicalagin showed inhibitory action against the 3CL-protease in a dose-dependent manner, and IC50 was found to be 6.192 μg/ml for punicalagin. Punicalagin (10 µg/mL) demonstrated a significant inhibitory activity toward 3CL-protease activity (p < 0.001), yet when punicalagin is combined with zinc sulfate monohydrate (punicalagin/Zn-II) extremely strong 3CL-protease activity (p < 0.001) was obtained. The action of 3CL-protease with punicalagin/Zn-II was decreased by approximately 4.4-fold in contrast to only punicalagin (10 µg/mL). Likewise, we did not notice any significant cytotoxicity caused by punicalagin, Zn-II, or punicalagin/Zn-II.

Conclusions: We suggest that these compounds could be used as potential antiviral drugs against COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology
  • COVID-19 / pathology
  • COVID-19 / virology
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Coronavirus 3C Proteases / antagonists & inhibitors
  • Coronavirus 3C Proteases / metabolism*
  • Drug Synergism
  • Humans
  • Hydrolyzable Tannins / chemistry*
  • Hydrolyzable Tannins / metabolism
  • Hydrolyzable Tannins / pharmacology
  • SARS-CoV-2 / enzymology*
  • SARS-CoV-2 / isolation & purification
  • Vero Cells
  • Zinc Sulfate / chemistry*
  • Zinc Sulfate / metabolism
  • Zinc Sulfate / pharmacology

Substances

  • Antiviral Agents
  • Hydrolyzable Tannins
  • punicalagin
  • Zinc Sulfate
  • 3C-like protease, SARS coronavirus
  • Coronavirus 3C Proteases