829 HEPATITIS C VIRUS AND LIPID DROPLETS: LIPIDOMIC PROFILING OF HCV CORE PROTEIN-EXPRESSING HEPATOMA CELLS

Abstract

2.9 (±0.4) and 0.52 (±0.08) uM, respectively. The CC50 of NDGA and M4N was 54 and >150uM, respectively. At the ED50, the CI of M4N with telaprevir was 0.66 and with boceprevir was 0.58. The CI of M4N with simvastatin was 0.50 and with fluvastatin was 0.48. The CI of M4N with NS5B nucleoside inhibitor 2’-C-methyladenosine was 0.48. Conclusion: Based on the EC50s and CC50s, M4N is a more potent compound than NDGA, roughly 5-fold throughout the three assays and has an improved selectivity index. The CIs show M4N to have moderate synergistic interactions with NS3 PIs, a NS5b nucleoside inhibitor, and with HMG-CoA reductase inhibitors. In conclusion, M4N and NDGA not only exhibit anti-HCV activity but also interact synergistically with other HCV antivirals making them an attractive candidate for HCV therapy. Moreover, NDGA derivatives will be novel antivirals through their action on cellular targets involved with lipid metabolism. Beneficial aspects of indirectly targeting viral replication in this manner include an expected high barrier to resistance and broad genotype coverage.