IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v465y2010i7294d10.1038_nature08960.html
   My bibliography  Save this article

Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect

Author

Listed:
  • Min Gao

    (Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA)

  • Richard E. Nettles

    (Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543, USA)

  • Makonen Belema

    (Department of Discovery Chemistry,)

  • Lawrence B. Snyder

    (Department of Discovery Chemistry,)

  • Van N. Nguyen

    (Department of Discovery Chemistry,)

  • Robert A. Fridell

    (Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA)

  • Michael H. Serrano-Wu

    (Department of Discovery Chemistry,)

  • David R. Langley

    (Department of Computer-Aided Drug Design,)

  • Jin-Hua Sun

    (Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA)

  • Donald R. O’Boyle II

    (Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA)

  • Julie A. Lemm

    (Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA)

  • Chunfu Wang

    (Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA)

  • Jay O. Knipe

    (Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA)

  • Caly Chien

    (Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543, USA)

  • Richard J. Colonno

    (Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA)

  • Dennis M. Grasela

    (Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543, USA)

  • Nicholas A. Meanwell

    (Department of Discovery Chemistry,)

  • Lawrence G. Hamann

    (Department of Discovery Chemistry,)

Abstract

New drugs for hepatitis C The development of direct-acting antiviral agents to treat chronic hepatitis C virus (HCV) infection, much needed clinically, has focused largely on inhibitors of two viral enzymes, the protease NS3 and NS5B, an RNA-dependent RNA polymerase essential for HCV replication. BMS-790052, identified using chemical genetics as a powerful specific HCV inhibitor, is a small-molecule inhibitor of a third viral molecule that has no known enzyme activity, the non-structural protein 5A (NS5A). A research team from Bristol-Myers Squibb this week reports on the discovery and virological profile of BMS-790052 and discloses clinical trial observations with this compound in normal healthy volunteers and HCV-infected subjects. These results establish proof-of-concept for HCV NS5A inhibition as a clinically relevant mechanism. In vitro data point to synergistic interactions with known HCV inhibitors, suggesting that cocktails of antiviral agents may be a viable therapeutic approach.

Suggested Citation

  • Min Gao & Richard E. Nettles & Makonen Belema & Lawrence B. Snyder & Van N. Nguyen & Robert A. Fridell & Michael H. Serrano-Wu & David R. Langley & Jin-Hua Sun & Donald R. O’Boyle II & Julie A. Lemm &, 2010. "Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect," Nature, Nature, vol. 465(7294), pages 96-100, May.
    • Handle: RePEc:nat:nature:v:465:y:2010:i:7294:d:10.1038_nature08960
    DOI: 10.1038/nature08960
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature08960
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature08960?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Libin Rong & Jeremie Guedj & Harel Dahari & Daniel J Coffield Jr & Micha Levi & Patrick Smith & Alan S Perelson, 2013. "Analysis of Hepatitis C Virus Decline during Treatment with the Protease Inhibitor Danoprevir Using a Multiscale Model," PLOS Computational Biology, Public Library of Science, vol. 9(3), pages 1-12, March.
    2. Tiffany Benzine & Ryan Brandt & William C Lovell & Daisuke Yamane & Petra Neddermann & Raffaele De Francesco & Stanley M Lemon & Alan S Perelson & Ruian Ke & David R McGivern, 2017. "NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains," PLOS Pathogens, Public Library of Science, vol. 13(6), pages 1-20, June.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:465:y:2010:i:7294:d:10.1038_nature08960. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.