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

doi:10.1021/acsinfecdis.5b00130

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

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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 language	English (US)
Pages (from-to)	173-179
Number of pages	7
Journal	ACS Infectious Diseases
Volume	2
Issue number	3
DOIs	https://doi.org/10.1021/acsinfecdis.5b00130
State	Published - Mar 11 2016

Keywords

Ebola virus
cathepsin inhibitor
filovirus
inhibition of host cell entry

ASJC Scopus subject areas

Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsinfecdis.5b00130

Cite this

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title = "Cysteine Cathepsin Inhibitors as Anti-Ebola Agents",

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.",

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AU - Schulze, Christopher J.

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AU - Dye, John M.

AU - Chandran, Kartik

AU - Bogyo, Matthew

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AB - 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.

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KW - filovirus

KW - inhibition of host cell entry

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Cysteine Cathepsin Inhibitors as Anti-Ebola Agents

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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