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 | |
| State | Published - Mar 11 2016 |
Fingerprint
Keywords
- cathepsin inhibitor
- Ebola virus
- filovirus
- inhibition of host cell entry
ASJC Scopus subject areas
- Infectious Diseases
Cite this
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 journal › Article
}
TY - JOUR
T1 - Cysteine Cathepsin Inhibitors as Anti-Ebola Agents
AU - Van Der Linden, Wouter A.
AU - Schulze, Christopher J.
AU - Herbert, Andrew S.
AU - Krause, Tyler B.
AU - Wirchnianski, Ariel A.
AU - Dye, John M.
AU - Chandran, Kartik
AU - Bogyo, Matthew
PY - 2016/3/11
Y1 - 2016/3/11
N2 - 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.
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.
KW - cathepsin inhibitor
KW - Ebola virus
KW - filovirus
KW - inhibition of host cell entry
UR - http://www.scopus.com/inward/record.url?scp=84969216967&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969216967&partnerID=8YFLogxK
U2 - 10.1021/acsinfecdis.5b00130
DO - 10.1021/acsinfecdis.5b00130
M3 - Article
VL - 2
SP - 173
EP - 179
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
SN - 2373-8227
IS - 3
ER -