Cysteine Cathepsin Inhibitors as Anti-Ebola Agents

Wouter A. Van Der Linden, Christopher J. Schulze, Andrew S. Herbert, Tyler B. Krause, Ariel A. Wirchnianski, John M. Dye, Kartik Chandran, Matthew Bogyo

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The recent Ebola virus outbreak in western Africa highlights the need for novel therapeutics that target Ebola virus and other filoviruses. Filoviruses require processing by host cell-derived cysteine cathepsins for productive infection. Here we report the generation of a focused library of cysteine cathepsin inhibitors and subsequent screening to identify compounds with potent activity against viral entry and replication. Our top compounds show highly potent and broad-spectrum activity against cysteine cathepsins and were able to effectively block entry of Ebola and Marburg viruses. These agents are promising leads for development as antifilovirus therapeutics.

Original languageEnglish (US)
Pages (from-to)173-179
Number of pages7
JournalACS Infectious Diseases
Volume2
Issue number3
DOIs
StatePublished - Mar 11 2016

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Ebolavirus
Cathepsins
Cysteine
Marburgvirus
Western Africa
Disease Outbreaks
Therapeutics
Infection

Keywords

  • cathepsin inhibitor
  • Ebola virus
  • filovirus
  • inhibition of host cell entry

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

Van Der Linden, W. A., Schulze, C. J., Herbert, A. S., Krause, T. B., Wirchnianski, A. A., Dye, J. M., ... Bogyo, M. (2016). Cysteine Cathepsin Inhibitors as Anti-Ebola Agents. ACS Infectious Diseases, 2(3), 173-179. https://doi.org/10.1021/acsinfecdis.5b00130

Cysteine Cathepsin Inhibitors as Anti-Ebola Agents. / Van Der Linden, Wouter A.; Schulze, Christopher J.; Herbert, Andrew S.; Krause, Tyler B.; Wirchnianski, Ariel A.; Dye, John M.; Chandran, Kartik; Bogyo, Matthew.

In: ACS Infectious Diseases, Vol. 2, No. 3, 11.03.2016, p. 173-179.

Research output: Contribution to journalArticle

Van Der Linden, WA, Schulze, CJ, Herbert, AS, Krause, TB, Wirchnianski, AA, Dye, JM, Chandran, K & Bogyo, M 2016, 'Cysteine Cathepsin Inhibitors as Anti-Ebola Agents', ACS Infectious Diseases, vol. 2, no. 3, pp. 173-179. https://doi.org/10.1021/acsinfecdis.5b00130
Van Der Linden WA, Schulze CJ, Herbert AS, Krause TB, Wirchnianski AA, Dye JM et al. Cysteine Cathepsin Inhibitors as Anti-Ebola Agents. ACS Infectious Diseases. 2016 Mar 11;2(3):173-179. https://doi.org/10.1021/acsinfecdis.5b00130
Van Der Linden, Wouter A. ; Schulze, Christopher J. ; Herbert, Andrew S. ; Krause, Tyler B. ; Wirchnianski, Ariel A. ; Dye, John M. ; Chandran, Kartik ; Bogyo, Matthew. / Cysteine Cathepsin Inhibitors as Anti-Ebola Agents. In: ACS Infectious Diseases. 2016 ; Vol. 2, No. 3. pp. 173-179.
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