Lomibuvir (Synonyms: VX-222)

Lomibuvir (VX-222), a selective, non-nucleoside polymerase inhibitor, targets thumb pocket 2 of the HCV NS5B polymerase (RdRp) with a Kd of 17 nM. Lomibuvir inhibits the 1b/Con1 HCV subgenomic replicon with an EC50 of 5.2 nM. Lomibuvir preferentially inhibits elongative RNA synthesis rather than de novo-initiated RNA synthesis[1].

Lomibuvir (VX-222) inhibits WT HCV 1b/Con1 replicon with an EC50 of 5.2 nM. Lomibuvir inhibits M423T, L419M and I482L (mutant replicons) with EC50s of 79.8, 563.1, 45.3 nM, respectively. Lomibuvir reduces de novo initiation slightly but also shows strong inhibition of primer extension. The IC50 of Lomibuvir for primer-extended RNA synthesis is 31 nM[1].Lomibuvir is a non-nucleoside, allosteric inhibitor of the hepatitis C virus NS5B polymerase[2].

[1]. Yi G, Deval J, et al. Biochemical study of the comparative inhibition of hepatitis C virus RNA polymerase by VX-222 and filibuvir. Antimicrob Agents Chemother. 2012;56(2):830-837. [2]. Li P, Dorsch W, et al. Discovery of Novel Allosteric HCV NS5B Inhibitors. 2. Lactam-Containing Thiophene Carboxylates. ACS Med Chem Lett. 2017;8(2):251-255. Published 2017 Jan 31. [3]. M. Rodriguez-Torres et al. SAFETY AND ANTIVIRAL ACTIVITY OF THE HCV NON-NUCLEOSIDE POLYMERASE INHIBITOR VX-222 IN TREATMENT-NAIVE GENOTYPE 1 HCV-INFECTED PATIENTS Journal of Hepatology Volume 52, Supplement 1 , Page S14, April 2010