In silico screening for potent inhibitors against the NS3/4A protease of hepatitis C virus.

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.

journal_name

Curr Pharm Des

authors

Meeprasert A,Rungrotmongkol T,Li MS,Hannongbua S

doi

10.2174/13816128113199990632

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

3465-77

issue

21

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-55718

journal_volume

20

pub_type

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