# Potential Activity of 6-Pentyl-α-pyrone as an Antiviral for Bovine Coronavirus

## TL;DR

This study shows that 6-pentyl-α-pyrone, a fungal compound, can reduce bovine coronavirus infection by inhibiting viral entry and affecting key proteins and signaling pathways.

## Contribution

The study demonstrates the antiviral activity of 6PP against BCoV and reveals its mechanism of action through AhR signaling and molecular docking.

## Key findings

- 6PP reduced viral yield and expression of viral spike and nucleocapsid proteins in infected cells.
- 6PP down-regulated the aryl hydrocarbon receptor (AhR) signaling pathway, a key modulator of CoV infection.
- Molecular docking showed 6PP binds to bovine AhR through hydrophobic interactions, suggesting a conserved mechanism.

## Abstract

During infection in vitro with the strain 438/06 of bovine coronavirus (BCoV), a β-coronavirus similar to severe acute respiratory syndrome (SARS) CoV-2, treatment with 6-pentyl-α-pyrone (6PP), a fungal metabolite obtained from Trichoderma atroviride, was recently shown to influence viral load by reducing viral entry. Herein, the ability of 6PP to counteract the BCoV infection was further investigated both in vitro and in silico. Following the BCoV (strain 282/23) infection in bovine (MDBK) cells, the 6PP in co-treatment increased cell viability, reduced morphological signs of cell death, and significantly inhibited viral yield, by lessening the expression of the viral spike (S) protein, as well as the gene transcription of the viral nucleocapsid (NP) protein. In addition, a noticeable down-regulation in the expression of aryl hydrocarbon receptor (AhR) signaling, a strategic modulator of CoVs infection, was found. Molecular docking studies were performed to evaluate the potential interaction between 6PP and AhR involved in the BCoV infection. The docking 3D structural model showed that 6PP fits into a binding pocket positioned between the PASB and TAD domains of bovine AhR (bAhR), where the ligand is stabilized through hydrophobic interactions. In addition, the obtained computational data strongly suggest that the bAhR binding mechanism of 6PP is principally mediated by a well-conserved hydrophobic cavity playing a key role in the modulation of the receptor functions. Overall, our findings showed an antiviral action of 6PP versus BCoV infection in vitro and in silico.