# Bioactive Compounds of Momordica charantia L. Downregulate the Protein Expression of ACE2 and TMPRSS2 In Vivo and In Vitro

## TL;DR

Bitter melon compounds reduce proteins that help SARS-CoV-2 enter cells, suggesting potential for natural prevention or treatment of COVID-19.

## Contribution

The study identifies bitter melon's bioactive compounds as potential inhibitors of SARS-CoV-2 cell entry mechanisms.

## Key findings

- Ethanol extract of bitter melon downregulates ACE2 and TMPRSS2 proteins in vitro and in vivo.
- Phytochemicals like p-coumaric acid, rutin, and quercetin show similar inhibitory effects.
- The compounds do not induce cytotoxicity, supporting their safety as natural agents.

## Abstract

The emergence of SARS-CoV-2, the etiological agent of COVID-19, has resulted in widespread global infection and millions of deaths. Viral entry is initiated by the interaction between the viral spike (S) protein and the host cell receptor ACE2, followed by TMPRSS2-mediated proteolytic activation that facilitates membrane fusion. Bitter melon (Momordica charantia L., MC), a traditional medicinal and edible plant widely used in tropical Asia, possesses notable anti-inflammatory, antioxidant, antitumor, and hypoglycemic properties. In this study, the ethanol extract of bitter melon (EMC) markedly downregulated ACE2 and TMPRSS2 expression in both in vitro and in vivo models without inducing cytotoxicity. Furthermore, phytochemicals isolated from EMC—including p-coumaric acid, rutin, and quercetin—exhibited comparable inhibitory effects. These results indicate that EMC and its bioactive constituents may interfere with SARS-CoV-2 entry by modulating the ACE2/TMPRSS2 axis, highlighting their potential as natural adjuncts for COVID-19 prevention or management.