Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations

Mélissanne de Wispelaere; Guangyan Du; Katherine A. Donovan; Tinghu Zhang; Nicholas A. Eleuteri; Jingting C. Yuan; Joann Kalabathula; Radosław P. Nowak; Eric S. Fischer; Nathanael S. Gray; Priscilla L. Yang

doi:10.1038/s41467-019-11429-w

Nature Communications (Aug 2019)

Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations

Mélissanne de Wispelaere,
Guangyan Du,
Katherine A. Donovan,
Tinghu Zhang,
Nicholas A. Eleuteri,
Jingting C. Yuan,
Joann Kalabathula,
Radosław P. Nowak,
Eric S. Fischer,
Nathanael S. Gray,
Priscilla L. Yang

Affiliations

Mélissanne de Wispelaere: Department of Microbiology and Blavatnik Institute, Harvard Medical School
Guangyan Du: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Katherine A. Donovan: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Tinghu Zhang: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Nicholas A. Eleuteri: Department of Cancer Biology, Dana-Farber Cancer Institute
Jingting C. Yuan: Department of Cancer Biology, Dana-Farber Cancer Institute
Joann Kalabathula: Department of Cancer Biology, Dana-Farber Cancer Institute
Radosław P. Nowak: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Eric S. Fischer: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Nathanael S. Gray: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Priscilla L. Yang: Department of Microbiology and Blavatnik Institute, Harvard Medical School

DOI: https://doi.org/10.1038/s41467-019-11429-w
Journal volume & issue: Vol. 10, no. 1
pp. 1 – 11

Abstract

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Targeted protein degradation (TPD) is a promising strategy for drug development. In this proof-of-concept study, the authors use telaprevir, which binds hepatitis C virus (HCV) NS3/4A protease, to target the protease for protein degradation, and show inhibition of wildtype as well as drug resistant HCV.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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