Literature DB >> 27347558

Cysteine Cathepsin Inhibitors as Anti-Ebola Agents.

Wouter A van der Linden1, Christopher J Schulze1, Andrew S Herbert2, Tyler B Krause3, Ariel A Wirchnianski2, John M Dye2, Kartik Chandran3, Matthew Bogyo1.   

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.

Entities:  

Keywords:  Ebola virus; cathepsin inhibitor; filovirus; inhibition of host cell entry

Year:  2016        PMID： 27347558      PMCID： PMC4918641          DOI： 10.1021/acsinfecdis.5b00130

Source DB:  PubMed          Journal:  ACS Infect Dis        ISSN： 2373-8227            Impact factor:   5.084


  18 in total

1.  Filoviruses require endosomal cysteine proteases for entry but exhibit distinct protease preferences.

Authors:  John Misasi; Kartik Chandran; Jin-Yi Yang; Bryden Considine; Claire Marie Filone; Marceline Côté; Nancy Sullivan; Giulia Fabozzi; Lisa Hensley; James Cunningham
Journal:  J Virol       Date:  2012-01-11       Impact factor: 5.103

2.  Design, synthesis, and evaluation of in vivo potency and selectivity of epoxysuccinyl-based inhibitors of papain-family cysteine proteases.

Authors:  Amir Masoud Sadaghiani; Steven H L Verhelst; Vasilena Gocheva; Kimberly Hill; Eva Majerova; Sherman Stinson; Johanna A Joyce; Matthew Bogyo
Journal:  Chem Biol       Date:  2007-05

3.  A forward genetic strategy reveals destabilizing mutations in the Ebolavirus glycoprotein that alter its protease dependence during cell entry.

Authors:  Anthony C Wong; Rohini G Sandesara; Nirupama Mulherkar; Sean P Whelan; Kartik Chandran
Journal:  J Virol       Date:  2010-01       Impact factor: 5.103

4.  Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection.

Authors:  Kartik Chandran; Nancy J Sullivan; Ute Felbor; Sean P Whelan; James M Cunningham
Journal:  Science       Date:  2005-04-14       Impact factor: 47.728

5.  Pathogenesis of experimental Ebola virus infection in guinea pigs.

Authors:  B M Connolly; K E Steele; K J Davis; T W Geisbert; W M Kell; N K Jaax; P B Jahrling
Journal:  J Infect Dis       Date:  1999-02       Impact factor: 5.226

6.  Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis.

Authors:  Johanna A Joyce; Amos Baruch; Kareem Chehade; Nicole Meyer-Morse; Enrico Giraudo; Fong-Ying Tsai; Doron C Greenbaum; Jeffrey H Hager; Matthew Bogyo; Douglas Hanahan
Journal:  Cancer Cell       Date:  2004-05       Impact factor: 31.743

7.  Improved quenched fluorescent probe for imaging of cysteine cathepsin activity.

Authors:  Martijn Verdoes; Kristina Oresic Bender; Ehud Segal; Wouter A van der Linden; Salahuddin Syed; Nimali P Withana; Laura E Sanman; Matthew Bogyo
Journal:  J Am Chem Soc       Date:  2013-09-19       Impact factor: 15.419

8.  Cathepsin B & L are not required for ebola virus replication.

Authors:  Andrea Marzi; Thomas Reinheckel; Heinz Feldmann
Journal:  PLoS Negl Trop Dis       Date:  2012-12-06

9.  Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection.

Authors:  Marceline Côté; John Misasi; Tao Ren; Anna Bruchez; Kyungae Lee; Claire Marie Filone; Lisa Hensley; Qi Li; Daniel Ory; Kartik Chandran; James Cunningham
Journal:  Nature       Date:  2011-08-24       Impact factor: 49.962

10.  CellProfiler: image analysis software for identifying and quantifying cell phenotypes.

Authors:  Anne E Carpenter; Thouis R Jones; Michael R Lamprecht; Colin Clarke; In Han Kang; Ola Friman; David A Guertin; Joo Han Chang; Robert A Lindquist; Jason Moffat; Polina Golland; David M Sabatini
Journal:  Genome Biol       Date:  2006-10-31       Impact factor: 13.583
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  19 in total

1.  Discovery of host-targeted covalent inhibitors of dengue virus.

Authors:  Mélissanne de Wispelaere; Margot Carocci; Yanke Liang; Qingsong Liu; Eileen Sun; Michael L Vetter; Jinhua Wang; Nathanael S Gray; Priscilla L Yang
Journal:  Antiviral Res       Date:  2016-12-26       Impact factor: 5.970

2.  Identification of a coumarin-based antihistamine-like small molecule as an anti-filoviral entry inhibitor.

Authors:  Han Cheng; Adam Schafer; Veronica Soloveva; Dima Gharaibeh; Tara Kenny; Cary Retterer; Rouzbeh Zamani; Sina Bavari; Norton P Peet; Lijun Rong
Journal:  Antiviral Res       Date:  2017-06-20       Impact factor: 5.970

Review 3.  Current status of small molecule drug development for Ebola virus and other filoviruses.

Authors:  Megan R Edwards; Christopher F Basler
Journal:  Curr Opin Virol       Date:  2019-04-16       Impact factor: 7.090

4.  Ebola Virus Entry Inhibitors.

Authors:  Ruikun Du; Qinghua Cui; Michael Caffrey; Lijun Rong
Journal:  Adv Exp Med Biol       Date:  2022       Impact factor: 2.622

5.  Phenotypic Prioritization of Diphyllin Derivatives That Block Filoviral Cell Entry by Vacuolar (H+ )-ATPase Inhibition.

Authors:  Aaron Lindstrom; Manu Anantpadma; Logan Baker; N M Raghavendra; Robert Davey; Vincent Jo Davisson
Journal:  ChemMedChem       Date:  2018-11-28       Impact factor: 3.466

6.  The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection.

Authors:  Elizabeth A Nelson; Julie Dyall; Thomas Hoenen; Alyson B Barnes; Huanying Zhou; Janie Y Liang; Julia Michelotti; William H Dewey; Lisa Evans DeWald; Richard S Bennett; Patrick J Morris; Rajarshi Guha; Carleen Klumpp-Thomas; Crystal McKnight; Yu-Chi Chen; Xin Xu; Amy Wang; Emma Hughes; Scott Martin; Craig Thomas; Peter B Jahrling; Lisa E Hensley; Gene G Olinger; Judith M White
Journal:  PLoS Negl Trop Dis       Date:  2017-04-12

Review 7.  Ebola Virus Entry: From Molecular Characterization to Drug Discovery.

Authors:  Cristiano Salata; Arianna Calistri; Gualtiero Alvisi; Michele Celestino; Cristina Parolin; Giorgio Palù
Journal:  Viruses       Date:  2019-03-19       Impact factor: 5.048

8.  Identification of Diaryl-Quinoline Compounds as Entry Inhibitors of Ebola Virus.

Authors:  Qinghua Cui; Han Cheng; Rui Xiong; Gang Zhang; Ruikun Du; Manu Anantpadma; Robert A Davey; Lijun Rong
Journal:  Viruses       Date:  2018-11-30       Impact factor: 5.048

9.  Characterization of Influenza Virus Pseudotyped with Ebolavirus Glycoprotein.

Authors:  Julie Huiyuan Xiao; Pramila Rijal; Lisa Schimanski; Arun Kumar Tharkeshwar; Edward Wright; Wim Annaert; Alain Townsend
Journal:  J Virol       Date:  2018-01-30       Impact factor: 5.103

10.  Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor.

Authors:  Qinghua Cui; Ruikun Du; Manu Anantpadma; Adam Schafer; Lin Hou; Jingzhen Tian; Robert A Davey; Han Cheng; Lijun Rong
Journal:  Viruses       Date:  2018-03-27       Impact factor: 5.048
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