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

[ Vol. 20 , Issue. 21 ]


Arthitaya Meeprasert, Thanyada Rungrotmongkol, Mai Suan Li and Supot Hannongbua   Pages 3465 - 3477 ( 13 )


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.


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


, , , Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, 254 Phayathai Road, Patumwan, Bangkok 10330, Thailand.

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