Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 1

PMID 28855547

Citations 13

Authors

Ying Wang

Sangwon Lee

Ya Ha

Wing Lam

Shao-Ru Chen

Ginger E Dutschman

Elizabeth A Gullen

Susan P Grill

Yao Cheng

Alois Furstner

Samson Francis

David C Baker

Xiaoming Yang

Kuo-Hsiung Lee

Yung-Chi Cheng

Affiliations

Soon will be listed here.

Abstract

Tylophorine analogs have been shown to exhibit diverse activities against cancer, inflammation, arthritis, and lupus in vivo. In this study, we demonstrated that two tylophorine analogs, DCB-3503 and rac-cryptopleurine, exhibit potent inhibitory activity against hepatitis C virus (HCV) replication in genotype 1b Con 1 isolate. The inhibition of HCV replication is at least partially mediated through cellular heat shock cognate protein 70 (Hsc70). Hsc70 associates with the HCV replication complex by primarily binding to the poly U/UC motifs in HCV RNA. The interaction of DCB-3503 and rac-cryptopleurine with Hsc70 promotes the ATP hydrolysis activity of Hsc70 in the presence of the 3' poly U/UC motif of HCV RNA. Regulating the ATPase activity of Hsc70 may be one of the mechanisms by which tylophorine analogs inhibit HCV replication. This study demonstrates the novel anti-HCV activity of tylophorine analogs. Our results also highlight the importance of Hsc70 in HCV replication.

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