Host soluble inositol phosphate signaling promotes coronavirus replication

Coronaviruses depend significantly on host pathways for replication, suggesting that targeting these host mechanisms could lead to effective antiviral therapies with lower chances of viral resistance. A team of researchers has now identified the host soluble inositol phosphate pathway as a previously unknown requirement for coronavirus infection.

Inhibiting or reducing activity within this pathway effectively curtails both alpha- and betacoronavirus replication, while enhancing the pathway's function boosts viral replication. The research team developed UNC7844, a powerful inhibitor targeting multiple kinases within this pathway, which reduces coronavirus replication by more than four orders of magnitude in lab-grown cells and suppresses infection in mice.

The mechanism of action involves inhibiting inositol (pyro)phosphate production, disrupting phosphoinositide homeostasis, and impairing late endosomal dynamics - all processes that are crucial for early post-entry steps of viral genome release and replication. The findings establish the soluble inositol (pyro)phosphate pathway as a key regulator of coronavirus infection and suggest that blocking its activity could be a promising strategy for host-directed antiviral treatments.