Applications of computer-aided approaches in the development of hepatitis C antiviral agents

作者：Ganesan Aravindhan; Barakat Khaled

来源：Expert Opinion on Drug Discovery, 2017, 12(4): 407-425.

DOI：10.1080/17460441.2017.1291628

• Molecular dynamics
• hepatitis C virus
• drug discovery
• direct acting agents
• computer-aided drug design
• protein flexibility
• QSAR
• binding free energy

Introduction: Hepatitis C virus (HCV) is a global health problem that causes several chronic lifethreatening liver diseases. The numbers of people affected by HCV are rising annually. Since 2011, the FDA has approved several anti-HCV drugs; while many other promising HCV drugs are currently in late clinical trials.
Areas covered: This review discusses the applications of different computational approaches in HCV drug design.
Expert opinion: Molecular docking and virtual screening approaches have emerged as a low-cost tool to screen large databases and identify potential small-molecule hits against HCV targets. Ligand-based approaches are useful for filtering-out compounds with rich physicochemical properties to inhibit HCV targets. Molecular dynamics (MD) remains a useful tool in optimizing the ligand-protein complexes and understand the ligand binding modes and drug resistance mechanisms in HCV. Despite their varied roles, the application of in-silico approaches in HCV drug design is still in its infancy. A more mature application should aim at modelling the whole HCV replicon in its active form and help to identify new effective druggable sites within the replicon system. With more technological advancements, the roles of computer-aided methods are only going to increase several folds in the development of next-generation HCV drugs.

• 出版日期2017