Fatty acid synthase and stearoyl-CoA desaturase-1 are conserved druggable cofactors of Old World Alphavirus genome replication

William Bakhache (1) , Aymeric Neyret (1) , Joe Mckellar (1) , Camille Clop (1) , Eric Bernard (1) , James Weger-Lucarelli (2) , Laurence Briant (1)

1 IRIM - Institut de Recherche en Infectiologie de Montpellier
2 Virginia Tech [Blacksburg]

Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne RNA virus that causes epidemics of debilitating disease in tropical and subtropical regions with autochtonous transmission in regions with temperate climate. Currently, there is no licensed vaccine or specific antiviral drug available against CHIKV infection. In this study, we examine the role, in the CHIKV viral cycle, of fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD1), two key lipogenic enzymes required for fatty acid production and early desaturation. We show that both enzymes and their upstream regulator PI3K are required for optimal CHIKV infection. We demonstrate that pharmacologic manipulation of FASN or SCD1 enzymatic activity by non-toxic concentrations of cerulenin or CAY10566 decreases CHIKV genome replication. Interestingly, a similar inhibitory effect was also obtained with Orlistat, an FDA

Mots clés: Chikungunya virus; Mayaro virus; lipid metabolism; fatty acid synthase; stearoyl-CoA desaturase-1; genome replication

Domaines: Interactions cellulaires [q-bio.CB]

William Bakhache, Aymeric Neyret, Joe Mckellar, Camille Clop, Eric Bernard, et al.. Fatty acid synthase and stearoyl-CoA desaturase-1 are conserved druggable cofactors of Old World Alphavirus genome replication. Antiviral Research, 2019, 172, pp.104642. ⟨10.1016/j.antiviral.2019.104642⟩. ⟨hal-02375405⟩