# The Emerging Promise of Pentacyclic Triterpenoid Derivatives as Novel Antiviral Agents Against SARS-CoV-2 Variants

## TL;DR

This paper explores how plant-derived compounds called pentacyclic triterpenoids may offer new antiviral treatments against SARS-CoV-2 variants, including Omicron.

## Contribution

The paper systematically reviews structure–activity relationships of PTs and proposes new strategies for multi-target inhibitors against SARS-CoV-2 variants.

## Key findings

- Pentacyclic triterpenoids inhibit multiple SARS-CoV-2 targets, including spike protein and RdRp.
- These compounds show broad-spectrum activity against variants from Alpha to Omicron.
- Structure–activity relationships suggest ways to design more effective multi-target inhibitors.

## Abstract

The continuous emergence of SARS-CoV-2 variants, especially the Omicron strain with its heightened transmissibility, has posed ongoing challenges to the efficacy of existing vaccine and drug regimens. This situation highlights the pressing demand for antiviral drugs employing novel mechanisms of action. Pentacyclic triterpenoids (PTs), a structurally varied group of compounds derived from plants, exhibit both antiviral and anti-inflammatory activities, making them attractive candidates for further therapeutic development. These natural products, along with their saponin derivatives, show broad-spectrum inhibitory effects against multiple SARS-CoV-2 variants (from Alpha to Omicron) via interactions with multiple targets, such as the spike protein, main protease (Mpro), RNA-dependent RNA polymerase (RdRp), and inflammatory signaling pathways. This review consolidates recent findings on PTs and their saponins, emphasizing their influence on the key structural features required for inhibiting viral attachment, membrane fusion, reverse transcription, and protease function. We systematically summarized the structure–activity relationships and their antiviral results of PTs based on different target proteins in existing studies. Furthermore, this work points toward new strategies for designing multi-target PT-based inhibitors with improved efficacy against Omicron and future variants.