A new natural α-helical peptide from the venom of the scorpion Heterometrus petersii kills HCV.
Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. There is no vaccine available for HCV, and almost half of patients cannot be cured using standard combination therapy. Thus, new anti-HCV strategies and drugs are urgently needed. Here, the gene encoding a new α-helical peptide, Hp1090, was screened from the venomous gland cDNA library of the scorpion Heterometrus petersii. Structural analysis showed that Hp1090 is an amphipathic α-helical peptide. In vitro HCV RNA inhibitory assays indicated that Hp1090 peptide inhibited HCV infection with an IC(50) of 7.62 μg/ml (5.0 μM), whereas Hp1035 peptide, showing high homology to Hp1090, exhibited no anti-HCV activity. Hp1090 acted as a viricide against HCV particles in vitro and prevented the initiation of HCV infection. Furthermore, this peptide interacted with HCV particles directly and rapidly permeabilized phospholipid membranes. Collectively, it seems that Hp1090 is virocidal for HCV in vitro, directly interacting with the viral membrane and decreasing the virus infectivity. These results suggest that Hp1090 could be considered an anti-HCV lead compound with virocidal mechanism that offers a potential therapeutic approach to HCV infection. Our work opens a new avenue for antiviral drug discovery in natural scorpion venom.
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Ran
R
Yan
Zhenhuan
Z
Zhao
Yawen
Y
He
Lin
L
Wu
Dawei
D
Cai
Wei
W
Hong
Yingliang
Y
Wu
Zhijian
Z
Cao
Congyi
C
Zheng
Wenxin
W
Li
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012604:Scorpion Venoms / Q000737:chemistry* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; C559117:Hp1090 peptide, Heterometrus petersii; D010455:Peptides; D012604:Scorpion Venoms