Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A

Jin-Hua Sun, Donald R. O’Boyle, Robert A. Fridell, David R. Langley, Chunfu Wang, Susan B. Roberts, Peter Nower, Benjamin M. Johnson, Frederic Moulin, Michelle J. Nophsker, Ying-Kai Wang, Mengping Liu, Karen Rigat, Yong Tu, Piyasena Hewawasam, John Kadow, Nicholas A. Meanwell, Mark Cockett, Julie A. Lemm, Melissa Kramer, Makonen Belema and Min Gao ()
Additional contact information
Jin-Hua Sun: Bristol-Myers Squibb Research and Development, 5 Research Parkway
Donald R. O’Boyle: Bristol-Myers Squibb Research and Development, 5 Research Parkway
Robert A. Fridell: Bristol-Myers Squibb Research and Development, 5 Research Parkway
David R. Langley: Computer-Assisted Drug Design, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Chunfu Wang: Bristol-Myers Squibb Research and Development, 5 Research Parkway
Susan B. Roberts: Bristol-Myers Squibb Research and Development, 5 Research Parkway
Peter Nower: Bristol-Myers Squibb Research and Development, 5 Research Parkway
Benjamin M. Johnson: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Frederic Moulin: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Michelle J. Nophsker: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Ying-Kai Wang: Leads Discovery and Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Mengping Liu: Bristol-Myers Squibb Research and Development, 5 Research Parkway
Karen Rigat: Bristol-Myers Squibb Research and Development, 5 Research Parkway
Yong Tu: Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Piyasena Hewawasam: Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway
John Kadow: Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Nicholas A. Meanwell: Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Mark Cockett: Bristol-Myers Squibb Research and Development, 5 Research Parkway
Julie A. Lemm: Bristol-Myers Squibb Research and Development, 5 Research Parkway
Melissa Kramer: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Makonen Belema: Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway
Min Gao: Bristol-Myers Squibb Research and Development, 5 Research Parkway

Nature, 2015, vol. 527, issue 7577, 245-248

Abstract: The drug daclatasvir (DCV), which inhibits the hepatitis C virus (HCV) non-structural protein 5A (NS5A), can successfully reduce viral load in patients; here, a combination of DCV and an NS5A analogue is shown to enhance DCV potency on multiple genotypes and overcome resistance in vitro and in a mouse model.

Date: 2015
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DOI: 10.1038/nature15711

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