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2017 Fiscal Year Final Research Report

Characterization of SPP involved in pathogenesis of HCV

Research Project

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Project/Area Number 15H04736
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionOsaka University

Principal Investigator

Matsuura Yoshiharu  大阪大学, 微生物病研究所, 教授 (50157252)

Co-Investigator(Renkei-kenkyūsha) OKAMOTO Toru  大阪大学, 微生物病研究所, 准教授 (80628595)
FUKUHARA Takasuke  大阪大学, 微生物病研究所, 准教授 (70598739)
Project Period (FY) 2015-04-01 – 2018-03-31
KeywordsSPP / HCV
Outline of Final Research Achievements

We have previously reported that the maturation of core protein of hepatitis C virus (HCV) by the cleavage with signal peptide peptidase (SPP) is essential for propagation of HCV. In this study, we examined the inhibitory activity of inhibitors for γ-secretase, another intramembrane cleaving protease, to SPP and revealed that interaction of Val223 in SPP with dibenzoazepine structure in the γ-secretase inhibitors is critical for inhibition of SPP. Treatment with SPP suppressed maturation of HCV core proteins of all genotypes of HCV and did not induce emergence of drug-resistant viruses. These results suggest that SPP is an ideal target for the development of therapeutics against chronic hepatitis C.

Free Research Field

ウイルス学

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Published: 2019-03-29  

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