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Research Article | Molecular Biology and Physiology

Avoiding Drug Resistance by Substrate Envelope-Guided Design: Toward Potent and Robust HCV NS3/4A Protease Inhibitors

Ashley N. Matthew, Jacqueto Zephyr, Desaboini Nageswara Rao, Mina Henes, Wasih Kamran, Klajdi Kosovrasti, Adam K. Hedger, Gordon J. Lockbaum, Jennifer Timm, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer
Richard Gerald Brennan, Editor
Ashley N. Matthew
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Jacqueto Zephyr
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Desaboini Nageswara Rao
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Mina Henes
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Wasih Kamran
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Klajdi Kosovrasti
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Adam K. Hedger
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Gordon J. Lockbaum
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Jennifer Timm
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Akbar Ali
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Nese Kurt Yilmaz
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Celia A. Schiffer
aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
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Richard Gerald Brennan
Duke University School of Medicine
Roles: Editor
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DOI: 10.1128/mBio.00172-20
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Article Information

DOI 
https://doi.org/10.1128/mBio.00172-20
PubMed 
32234812

Published By 
American Society for Microbiology
History 
  • Received January 31, 2020
  • Accepted February 11, 2020
  • Published online March 31, 2020.

Copyright & Usage 
Copyright © 2020 Matthew et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Editors and / or Reviewers 
  • Richard Gerald Brennan, Editor, Duke University School of Medicine

Author Information

  1. Ashley N. Matthewa,
  2. Jacqueto Zephyra,
  3. Desaboini Nageswara Raoa,
  4. Mina Henesa,
  5. Wasih Kamrana,
  6. Klajdi Kosovrastia,
  7. Adam K. Hedgera,
  8. Gordon J. Lockbauma,
  9. Jennifer Timma,
  10. Akbar Alia,
  11. Nese Kurt Yilmaza,
  12. Celia A. Schiffera
  1. aDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
  • Address correspondence to Nese Kurt Yilmaz, Nese.KurtYilmaz{at}umassmed.edu, or Celia A. Schiffer, Celia.Schiffer{at}umassmed.edu.
  • Ashley N. Matthew and Jacqueto Zephyr contributed equally to this work. Author order was determined both alphabetically and in order of decreasing seniority.

  • Citation Matthew AN, Zephyr J, Nageswara Rao D, Henes M, Kamran W, Kosovrasti K, Hedger AK, Lockbaum GJ, Timm J, Ali A, Kurt Yilmaz N, Schiffer CA. 2020. Avoiding drug resistance by substrate envelope-guided design: toward potent and robust HCV NS3/4A protease inhibitors. mBio 11:e00172-20. https://doi.org/10.1128/mBio.00172-20.

  1. This article is a direct contribution from Celia A. Schiffer, a Fellow of the American Academy of Microbiology, who arranged for and secured reviews by Stefan Sarafianos, Emory University, and Matthias Gotte, University of Alberta.

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Avoiding Drug Resistance by Substrate Envelope-Guided Design: Toward Potent and Robust HCV NS3/4A Protease Inhibitors
Ashley N. Matthew, Jacqueto Zephyr, Desaboini Nageswara Rao, Mina Henes, Wasih Kamran, Klajdi Kosovrasti, Adam K. Hedger, Gordon J. Lockbaum, Jennifer Timm, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer
mBio Mar 2020, 11 (2) e00172-20; DOI: 10.1128/mBio.00172-20

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Avoiding Drug Resistance by Substrate Envelope-Guided Design: Toward Potent and Robust HCV NS3/4A Protease Inhibitors
Ashley N. Matthew, Jacqueto Zephyr, Desaboini Nageswara Rao, Mina Henes, Wasih Kamran, Klajdi Kosovrasti, Adam K. Hedger, Gordon J. Lockbaum, Jennifer Timm, Akbar Ali, Nese Kurt Yilmaz, Celia A. Schiffer
mBio Mar 2020, 11 (2) e00172-20; DOI: 10.1128/mBio.00172-20
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KEYWORDS

X-ray crystallography
drug design
drug resistance mechanisms
hepatitis C virus
structural biology

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