Elbasvir (MK-8742)

Elbasvir is a direct-acting antiviral drug that potently inhibits hepatitis C virus (HCV) non-structural protein 5A (NS5A) with an EC₅₀ value of 2.2 pM in Huh7 human liver cancer cells expressing pH77S.3/GLuc2A, a cell-culture adapted HCV16 genotype 1a derivative and luciferase reporter, following a 48-hour exposure in vitro.^1,2 NS5A is essential for HCV RNA synthesis and viral assembly, and elbasvir inhibits the assembly of new viral replicase complexes when used at a concentration of 50 pM.² It exhibits potent inhibitory activity against a broad range of HCV genotypes with EC₅₀ values of 0.0002-34 nM in Huh7 cells expressing replicons of HCV genotype 4 NS5A and EC₅₀ values of less than 0.2 nM for replicons from all other tested genotypes except 2b.^3,1,4 Formulations containing elbasvir have been used alone and in combination with NS3/4A protease inhibitors in the treatment of HCV.

1.Lahser, F.C., Bystol, K., Curry, S., et al.The combination of grazoprevir, a Hepatitis C virus (HCV) NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor, demonstrates a high genetic barrier to resistance in HCV genotype 1a repliconsAntimicrob. Agents Chemother.60(5)2954-2964(2016) 2.McGivern, D.R., Masaki, T., Williford, S., et al.Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitorsGastroenterology147(2)453-462(2014) 3.Asante-Appiah, E., Curry, S., McMonagle, P., et al.Antiviral activity and resistance analysis of NS3/4A protease inhibitor grazoprevir and NS5A inhibitor elbasvir in Hepatitis C virus GT4 repliconsAntimicrob. Agents Chemother.61(7)e00363-e00417(2017) 4.Liu, R., Curry, S., McMonagle, P., et al.Susceptibilities of genotype 1a, 1b, and 3 hepatitis C virus variants to the NS5A inhibitor elbasvirAntimicrob. Agents Chemother.59(11)6922-6929(2015)