Farnesoid X receptor agonists as broad-acting antivirals: Evidence from hepatitis viruses and beyond?

As intracellular organisms, viruses exploit host metabolism to replicate and propagate. The farnesoid X receptor alpha (FXRα) is a bile acid-activated nuclear receptor that regulates bile acid, glucose and lipid metabolism, as well as inflammation and immunity. Since its discovery in 1995, numerous ligands have been developed to treat metabolism-related syndromes. More recently, FXRα has been shown to modulate the life cycle of various viruses that infect human. This review provides a comprehensive summary of the literature regarding the effect of FXRα agonism in viral infections caused by hepatotropic viruses, enteric viruses and other viral pathogens. Rather than acting through a single antiviral mechanism, FXRα has been reported to influence many steps of viral replication, including entry, transcription and particle secretion. The established safety profiles of FXRα agonists and their clinical use for other pathologies could pave the way for their re-purposing as broad-spectrum antivirals.