# Antiviral Efficacy of Lignan Derivatives (-)-Asarinin and Sesamin Against Foot-and-Mouth Disease Virus by Targeting RNA-Dependent RNA Polymerase (3Dpol)

## TL;DR

Researchers found that two plant compounds, (-)-asarinin and sesamin, can stop the foot-and-mouth disease virus by blocking its replication enzyme.

## Contribution

This study is the first to show that lignan derivatives inhibit FMDV replication by targeting its RNA-dependent RNA polymerase.

## Key findings

- (-)-Asarinin and sesamin inhibit FMDV replication in cell culture with EC50 values of 15.11 μM and 52.98 μM, respectively.
- Both compounds reduce negative-strand RNA production and suppress viral replication in a dose-dependent manner.
- In silico analysis confirms that the lignans bind to the active site of FMDV 3Dpol.

## Abstract

Foot-and-mouth disease (FMD) is a highly contagious viral disease that severely impacts livestock worldwide, causing major economic losses. Our research explored new ways to combat this virus using natural compounds. We investigated two plant-derived compounds called (-)-asarinin and sesamin and discovered that they are highly effective at stopping the FMD virus in cell culture. In our study, we found that these two compounds work by targeting and disabling a key part of the virus’s machinery, specifically an enzyme it needs to replicate itself. By blocking this “copying machine” (known as 3Dpol), (-)-asarinin and sesamin prevent the virus from multiplying and spreading. This discovery represents a significant step toward developing new and effective antiviral treatments that could help protect livestock and control the spread of foot-and-mouth disease.

Foot-and-mouth disease (FMD) is a highly contagious viral infection affecting livestock. Although inactivated vaccines are commonly used, their effectiveness is limited by an immunity gap. Therefore, complementary antiviral strategies are required for effective control and prevention. Lignans, plant-derived compounds, have shown promising antiviral properties, yet their potential against foot-and-mouth disease virus (FMDV) remains underexplored. This study employed virtual screening to identify lignan compounds targeting viral RNA-dependent RNA polymerase (3Dpol). Six lignan compounds were selected for cytotoxicity and antiviral activity evaluation including pre-viral entry, post-viral entry, and protective effect assays. Antiviral activity assay showed that (-)-asarinin and sesamin exhibit potent inhibition effects in the post-viral entry with EC50 of 15.11 μM and 52.98 μM, respectively, using immunoperoxidase monolayer assay. Both compounds exhibited dose-dependent reduction in viral replication with significant suppression of negative-strand RNA production. Lignans’ ability to target FMDV 3Dpol was further confirmed using a cell-based FMDV minigenome assay. Among the tested lignans, (-)-asarinin demonstrated remarkable inhibition of GFP expression (IC50 value at 10.37 μM), while sesamin required a higher concentration for similar effects. In silico prediction revealed that these lignans preferentially bind to FMDV 3Dpol active site. These findings are the first to establish (-)-asarinin and sesamin as promising antiviral candidates against FMDV.