In Silico Screening for Potent Inhibitors against the NS3/4A Protease of Hepatitis C Virus

Title:In Silico Screening for Potent Inhibitors against the NS3/4A Protease of Hepatitis C Virus

Volume: 20 Issue: 21

Author(s): Arthitaya Meeprasert, Thanyada Rungrotmongkol, Mai Suan Li and Supot Hannongbua

Affiliation:

Keywords: NS3/4A protease, hepatitis C virus, steered molecular dynamics simulations.

Abstract: Hepatitis C virus (HCV) infections are a serious viral health problem globally, causing liver cirrhosis and inflammation that can develop to hepatocellular carcinoma and death. Since the HCV NS3/4A protease complex cleaves the scissile peptide bond in the viral encoded polypeptide to release the non-structural proteins during the viral replication process, this protease is then an important target for drug design. The computer-aided drug design and screening targeted at NS3/4A protease of HCV were reviewed. In addition, using steered molecular dynamics simulations, potent inhibitors of the NS3/4A complex were searched for by screening the ZINC database based upon the hypothesis that a high rupture force indicates a high binding efficiency. Nine top-hit compounds (59500093, 59784724, 13527817, 26660256, 29482733, 25977181, 28005928, 13527826 and 13527826) were found that had the same or a greater maximum rupture force (and so assumed binding strength and inhibitory potency) than the four current drugs and so are potential candidates as anti- HCV chemotherapeutic agents. In addition, van der Waals interactions were found to be the main contribution in stabilizing the ligand- NS3/4A complex.

Cite this article as:

Meeprasert Arthitaya, Rungrotmongkol Thanyada, Li Suan Mai and Hannongbua Supot, In Silico Screening for Potent Inhibitors against the NS3/4A Protease of Hepatitis C Virus, Current Pharmaceutical Design 2014; 20 (21) . https://dx.doi.org/10.2174/13816128113199990632