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

M.J. Saadh, A.M. Almaaytah, M. Alaraj, M.F. Dababneh, I. Sa’adeh, S.M. Aldalaen, A.M. Kharshid, A. Alboghdadly, M. Hailat, A. Khaleel, K.D. Al-Hamaideh, W. Abu Dayyih

Faculty of Pharmacy, Middle East University, Amman, Jordan. msaadeh@meu.edu.jo

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• Infectious Diseases

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.

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