title: Antiviral activity of peptide inhibitors derived from the protein E stem against Japanese encephalitis and Zika viruses.
abstract: Japanese encephalitis virus (JEV) and Zika virus (ZIKV) are mosquito-borne viruses of the Flavivirus genus that cause viral encephalitis and congenital microcephaly, respectively, in humans, and thus present a risk to global public health. The envelope glycoprotein (E protein) of flaviviruses is a class II viral fusion protein that mediates host cell entry through a series of conformational changes, including association between the stem region and domain II leading to virion-target cell membrane fusion. In this study, peptides derived from the JEV E protein stem were investigated for their ability to block JEV and ZIKV infection. Peptides from stem helix 2 inhibit JEV infection with the 50% inhibitory concentration (IC50) in the nanomolar range. One of these peptides (P5) protected mice against JEV-induced lethality by decreasing viral load, while abrogating histopathological changes associated with JEV infection. We also found that P5 blocked ZIKV infection with IC50at the micromolar level. Moreover, P5 was proved to reduce the histopathological damages in brain and testes resulting from ZIKV infection in type I and II interferon receptor-deficient (AG6) mice. These findings provide a basis for the development of peptide-based drugs against JEV and ZIKV.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Liman
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Peilin
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Qilin
authors.initials: Q
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Leike
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China.
authors.forename: Gengfu
authors.initials: G
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China; University of the Chinese Academy of Sciences, Beijing, China. Electronic address: wangwei@wh.iov.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000821:virology; D002460:Cell Line; D004664:Encephalitis Virus, Japanese / Q000737:chemistry / Q000187:drug effects*; D004672:Encephalitis, Japanese / Q000188:drug therapy / Q000821:virology; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013737:Testis / Q000187:drug effects / Q000473:pathology / Q000821:virology; D014760:Viral Fusion Proteins / Q000737:chemistry*; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D000071244:Zika Virus
chemical_list: D000998:Antiviral Agents; D010446:Peptide Fragments; D014760:Viral Fusion Proteins
keywords: Glycoprotein; Japanese encephalitis virus; Peptide inhibitors; Stem; Zika virus