Inhibitory Activity of a Scorpion Defensin BmKDfsin3 Against Hepatitis C Virus

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2020 Jan 23

PMID 31963532

Citations 9

Authors

Yuting Cheng

Fang Sun

Songryong Li

Minjun Gao

Luyao Wang

Moustafa Sarhan

Mohamed A Abdel-Rahman

Wenxin Li

Hang Fai Kwok

Yingliang Wu

Zhijian Cao

Affiliations

Soon will be listed here.

Abstract

Hepatitis C virus (HCV) infection is a major worldwide health problem which can cause chronic hepatitis, liver fibrosis and hepatocellular carcinoma (HCC). There is still no vaccine to prevent HCV infection. Currently, the clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) which are expensive and have side effects. Here, BmKDfsin3, a scorpion defensin from the venom of Karsch, is found to dose-dependently inhibit HCV infection at noncytotoxic concentrations and affect viral attachment and post-entry in HCV life cycle. Further experimental results show that BmKDfsin3 not only suppresses p38 mitogen-activated protein kinase (MAPK) activation of HCV-infected Huh7.5.1 cells, but also inhibits p38 activation of Huh7.5.1 cells stimulated by tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) or lipopolysaccharide (LPS). BmKDfsin3 is also revealed to enter into cells. Using an upstream MyD88 dimerization inhibitor ST2345 or kinase IRAK-1/4 inhibitor I, the inhibition of p38 activation represses HCV replication in vitro. Taken together, a scorpion defensin BmKDfsin3 inhibits HCV replication, related to regulated p38 MAPK activation.

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