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

Wang, Ying; Lee, Sangwon; Lam, Wing; Chen, Shao-Ru; Dutschman, Ginger E.; Gullen, Elizabeith A.; Grill, Susan P.; Cheng, Yao; Fürstner, Alois; Francis, Samson; Baker, David C.; Yang, Xiaoming; Lee, Kuo-Hsiung; Cheng, Yung-Chi

doi:10.1038/s41598-017-08815-z

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

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

MPS-Authors

/persons/resource/persons58380

Fürstner, Alois
Research Department Fürstner, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

[367]SI.pdf
(Supplementary material), 2MB

Citation

Wang, Y., Lee, S., Lam, W., Chen, S.-R., Dutschman, G. E., Gullen, E. A., et al. (2017). Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication. Scientific Reports, 7: 10037. doi:10.1038/s41598-017-08815-z.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002D-F558-F

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.