# Identification and characterization of a nonpeptidic cyclophilin ligand with antiviral activity against feline and porcine α-coronaviruses

## TL;DR

Researchers found a new antiviral compound that can inhibit the replication of several coronaviruses in animals, potentially offering a treatment for both veterinary and zoonotic infections.

## Contribution

A novel nonpeptidic cyclophilin ligand, F83233, was identified as a broad-spectrum antiviral against feline and porcine α-coronaviruses.

## Key findings

- F83233 effectively inhibits replication of FIPV, TGEV, and PEDV at micromolar concentrations.
- The compound works in feline, porcine, and simian cells, suggesting broad applicability.
- Cyclophilin targeting may offer a strategy for antiviral therapies against multiple CoVs.

## Abstract

Coronaviruses (CoVs) are emerging pathogens that have been extensively studied over the last twenty years and can cause acute respiratory diseases in humans, as exemplified by the SARS-CoV-2 pandemic. CoVs are also known for their importance in veterinary medicine and are responsible for severe pathologies in pets and livestock. These include feline infectious peritonitis virus (FIPV), which causes fatal disease in cats. In livestock, porcine CoVs such as transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhoea virus (PEDV) are the causative agents of acute enteric disease in piglets, which has a high mortality rate and a significant impact on the pork industry. In addition, animal CoVs may represent zoonotic reservoirs. Therefore, efficient antiviral strategies are needed to inhibit the replication of CoVs that infect various animal species. Here, we synthesized twenty small-molecule ligands that target cyclophilins, a family of cellular chaperones hijacked by several viruses, including CoVs. We screened their antiviral activity against feline and porcine α-CoVs and identified F83233 as a potent inhibitor of FIPV, TGEV and PEDV replication at micromolar concentrations that was effective in feline, porcine, and simian cells. As cyclophilins are highly conserved among mammals, F83233 could be a promising antiviral to treat different animal and zoonotic CoVs.