Evacetrapib
Chikungunya virus is sensitive to evacetrapib in cell culture, but through an off-target effect independent of CETP itself (Viruses 2025)
Original title: Chikungunya Replication and Infection Is Dependent upon and Alters Cellular Hexosylceramide Levels in Vero Cells
A cell-culture study used untargeted lipidomics to show that chikungunya virus (CHIKV) infection markedly reduces hexosylceramide levels in Vero cells while increasing ceramide byproducts, and that CHIKV replication depends on fatty acid synthesis, beta-oxidation and glycosphingolipid biosynthesis. Inhibiting UGT8, needed for galactosylceramide production, significantly impaired CHIKV replication and entry, reproduced in mouse hepatocytes. CHIKV was also sensitive to evacetrapib, a CETP inhibitor, but the authors report the inhibitory mechanism appeared independent of CETP itself, suggesting an off-target antiviral effect rather than a CETP-mediated one. Preclinical cell-culture work identifying glycosphingolipid metabolism, not CETP inhibition, as the pathway of therapeutic interest for CHIKV.
Original abstract
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes significant global morbidity, including fever, rash, and persistent arthralgia. Utilizing untargeted lipidomics, we investigated how CHIKV infection alters host cell lipid metabolism in Vero cells. CHIKV infection induced marked catabolism of hexosylceramides, reducing their levels while increasing ceramide byproducts. Functional studies revealed a reliance on fatty acid synthesis, β-oxidation, and glycosphingolipid biosynthesis. Notably, inhibition of uridine diphosphate glycosyltransferase 8 (UGT8), essential for galactosylceramide production, significantly impaired CHIKV replication and entry in Vero cells. Sensitivity of CHIKV to UGT8 inhibition was reproduced in a disease-relevant cell line, mouse hepatocytes (Hepa1-6). CHIKV was also sensitive to evacetrapib, a cholesterol ester transfer protein (CETP) inhibitor, though the mechanism of inhibition appeared independent of CETP itself, suggesting an off-target effect. These findings highlight specific lipid pathways, particularly glycosphingolipid metabolism, as critical for CHIKV replication and further refine our understanding of how CHIKV exploits host lipid networks. This study provides new insights into CHIKV biology and suggests that targeted investigation of host lipid pathways may inform future therapeutic strategies.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.