Long-chain fatty acyl-coenzyme A suppresses hepatitis C virus infection by targeting virion-bound lipoproteins

In this study, we identified the antiviral effects of long-chain fatty acyl-coenzyme A (LCFA-CoA) against the infections of HCV genotypes 1–6 through targeting mature HCV-bound lipoproteins, suggesting novel mechanism(s) of antiviral different from those used by host-targeting agents or DAAs. We found that the antiviral activity of LCFA-CoA relied on the long-chain saturated fatty acid and the CoA group, and was enhanced when combined with pegylated-interferon or DAAs. Importantly, we demonstrated that LCFA-CoA efficiently inhibited the infection of HCV variants carrying DAA-resistant mutations. The mechanistic study revealed that LCFA-CoA specifically abolished the attachment and binding steps and also inhibited the cell-to-cell viral transmission. LCFA-CoA targeted mature HCV-bound lipoproteins, but not apolipoproteins B or E. In addition, LCFA-CoA could also inhibit the infection of the dengue virus. Our findings suggest that LCFA-CoA could potentially serve as a supplement HCV therapy, particularly for the DAA-resistant HCV variants. Taken together, LCFA-CoA may be further developed to be a novel class of antivirals with mechanism(s), different from host-targeting agents or DAAs, of targeting the components associated with mature HCV virions.
Source: Antiviral Therapy - Category: Virology Source Type: research