NS5A as a Target for HCV Drug Discovery

  • Donald R. O’BoyleII
  • Min GaoEmail author
Part of the Topics in Medicinal Chemistry book series (TMC, volume 32)


Discovery and development of HCV inhibitors is one of the most successful stories in the history of antiviral research. After more than 30 years of effort by academic and pharmaceutical researchers, HCV infection is a curable disease. In fact, HCV is the first chronic infectious disease to be cured with combinations of direct antiviral agents. Among these antiviral agents, NS5A inhibitors are the most potent. The unprecedented low pM potency, pan-genotype coverage, and well-tolerated clinical profile have made NS5A inhibitors an essential component of all interferon-/ribavirin-free regimens in currently approved HCV therapies. Since NS5A has no known enzymatic activity and is not a traditional antiviral target, this review focuses on the challenges and concerns that arose during the discovery of this class of inhibitor, the mode of action/inhibition, and the value of NS5A inhibitors in the treatment of HCV infection.


Combination therapy Daclatasvir Genotype coverage NS5A inhibitors Resistance Synergistic effect 



We thank Drs David Langley for providing Fig. 1 and Susan Roberts for critical review and editing the manuscript.

Compliance with Ethical Standards

Conflict of Interest: Dr. Gao worked for Bristol Myers Squibb.

Ethical Approval: This chapter does not contain any studies with human participants or animals performed by any of the authors.


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© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Bristol-Myers Squibb CompanyPenningtonUSA
  2. 2.Arbutus BioPharmaWarminsterUSA

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