# Dose-dependent antiviral effects of glycyrrhizin, curcumin, and harmaline against clinical SARS-CoV-2 isolates, including D614G, Omicron BA.5, and Omicron XBB.1

## TL;DR

This study shows that three natural compounds can effectively neutralize multiple SARS-CoV-2 variants in lab tests, suggesting potential as broad-spectrum treatments for COVID-19.

## Contribution

The study demonstrates the variant-independent antiviral activity of glycyrrhizin, curcumin, and harmaline against multiple SARS-CoV-2 isolates.

## Key findings

- Glycyrrhizin, curcumin, and harmaline effectively neutralized SARS-CoV-2 D614G, Omicron BA.5, and Omicron XBB.1 at subtoxic concentrations.
- The tested compounds showed potent antiviral activity across all tested variants, indicating variant-independent efficacy.
- (-)-Epigallocatechin showed antiviral activity but was less effective compared to the other three compounds.

## Abstract

SARS-CoV-2 remains a major global health challenge, as infection can lead to potential life-threatening conditions such as COVID-19. Emerging variants of the virus are characterized by higher transmission rates and immune escape mutations, enabling them to evade vaccine-induced immunity. Existing treatment options, including monoclonal antibodies, are often variant-specific and not widely accessible, especially in low- and middle-income countries. Natural compounds derived from medicinal herbs and green tea have demonstrated antiviral activity against various viruses and may offer promising, variant-independent therapeutic potential.

In this study, we examined the antiviral activity of four plant-derived compounds: glycyrrhizin, curcumin, harmaline, and (-)-epigallocatechin. The compounds were tested in vitro against SARS-CoV-2 D614G, Omicron BA.5, and Omicron XBB.1. The antiviral efficacy was assessed at subtoxic concentrations to evaluate potential therapeutic applicability.

All tested compounds showed effective neutralization of SARS-CoV-2 D614G, Omicron BA.5, and Omicron XBB.1 at subtoxic concentrations. In particular, glycyrrhizin, curcumin, and harmaline exhibited potent antiviral activity across all tested variants.

Our findings support the potential of glycyrrhizin, curcumin, and harmaline as variant-independent treatment candidates for COVID-19. However, further clinical studies are necessary to validate their efficacy and safety in vivo.