Bithiazole inhibitors of PI4KB show broad-spectrum antiviral activity against different viral families

Le résumé fourni par la source

Broad-spectrum antivirals can be extremely important for pandemic preparedness. Targeting host factors dispensable for the host but indispensable for the virus can result in high barrier to resistance and a large range of viruses targeted. PI4KB is a lipid kinase involved in the replication of several RNA viruses, but common inhibitors of this target are mainly active against members of the Picornaviridae family. Herein we describe the optimization of bithiazole PI4KB inhibitors as broad-spectrum antivirals (BSAs) active against different members of the Picornaviridae , Coronaviridae , Flaviviridae and Poxviridae families. Since some of these viruses are transmitted via respiratory route, the efficacy of one of the most promising compounds was evaluated in an airway model. The molecule showed complete viral inhibition and absence of toxicity. These results pave the road for the development of new BSAs. • Bithiazoles, PI4KB inhibitors, exhibit a broad-spectrum antiviral activity. • Bithiazoles activity on rhinovirus is PI4KB dependent and synergistic with rupintrivir. • Bithiazoles retain activity in human derived respiratory tissues.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.