Nonstructural protein 5A (NS5A) protein of hepatitis C virus (HCV) can regulate the ability of host cells to respond to interferon (IFN). Meanwhile, NS5A is an RNA binding phosphoprotein composed of N-terminal membrane anchor (AH), domain 1 (D1), and two essentially disordered domains (D2 and D3). As a NS protein with no significant enzymatic activity, NS5A functions by interacting with other viruses and cellular proteins. Nonetheless, NS5A plays multiple roles in mediating viral replication, host cell interactions, and viral pathogenesis. NS5A directly binds to viral RNA, but also regulates HCV RNA replication by interacting with other NS proteins and various cytokines. Besides, HCV is the main cause of liver disease. The phosphorylation state of NS5A has a significant impact on its function and virus life cycle. In addition, NS5A inhibitors represent a new class of direct acting antiviral drugs. Here, we will introduce a potent hepatitis C virus protein NS5A Inhibitor, Ombitasvir.

Ombitasvir is a Potent Hepatitis C Virus Protein NS5A Inhibitor for Chronic Hepatitis C Research.

First of all, Ombitasvir (ABT-267) is a potent inhibitor of the hepatitis C virus protein NS5A, with EC50s of 0.82 to 19.3 pM against HCV genotypes 1 to 5, and 366 pM against genotype 6a. Moreover, Ombitasvir is active against the genotype 2a JFH-1 replicon, with an EC50 of 0.82 pM.

In the second place, In GT1a, variants M28V, L31V, and H58D confers 58- to 243-fold resistance to Ombitasvir. Furthermore, single variants M28T, Q30R, and Y93C/S confers 800- to 8965-fold resistance, while Y93H/N confers >40000-fold resistance to Ombitasvir. Particularly, Ombitasvir has favorable pharmacokinetic characteristics.

All in all, Ombitasvir is a potent hepatitis C virus protein NS5A inhibitor for chronic hepatitis C research.


[1] Krishnan P, et al. Antimicrob Agents Chemother. 2015 Feb;59(2):979-87