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A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles

Viral infections still threaten human health all over the world, and many people die from viral diseases every year. However, there are no effective vaccines or drugs for preventing or managing most viral diseases. Thus, the discovery and development of broad-spectrum antiviral agents remain urgent....

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Autores principales: Li, Fangfang, Lang, Yange, Ji, Zhenglin, Xia, Zhiqiang, Han, Yuewen, Cheng, Yuting, Liu, Gaomin, Sun, Fang, Zhao, Yonghui, Gao, Minjun, Chen, Zongyun, Wu, Yingliang, Li, Wenxin, Cao, Zhijian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322876/
https://www.ncbi.nlm.nih.gov/pubmed/30404919
http://dx.doi.org/10.1074/jbc.RA118.005015
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author Li, Fangfang
Lang, Yange
Ji, Zhenglin
Xia, Zhiqiang
Han, Yuewen
Cheng, Yuting
Liu, Gaomin
Sun, Fang
Zhao, Yonghui
Gao, Minjun
Chen, Zongyun
Wu, Yingliang
Li, Wenxin
Cao, Zhijian
author_facet Li, Fangfang
Lang, Yange
Ji, Zhenglin
Xia, Zhiqiang
Han, Yuewen
Cheng, Yuting
Liu, Gaomin
Sun, Fang
Zhao, Yonghui
Gao, Minjun
Chen, Zongyun
Wu, Yingliang
Li, Wenxin
Cao, Zhijian
author_sort Li, Fangfang
collection PubMed
description Viral infections still threaten human health all over the world, and many people die from viral diseases every year. However, there are no effective vaccines or drugs for preventing or managing most viral diseases. Thus, the discovery and development of broad-spectrum antiviral agents remain urgent. Here, we expressed and purified a venom peptide, Ev37, from the scorpion Euscorpiops validus in a prokaryotic system. We found that rEv37 can inhibit dengue virus type 2 (DENV-2), hepatitis C virus (HCV), Zika virus (ZIKV), and herpes simplex virus type 1 (HSV-1) infections in a dose-dependent manner at noncytotoxic concentrations, but that it has no effect on Sendai virus (SeV) and adenovirus (AdV) infections in vitro. Furthermore, rEv37 alkalized acidic organelles to prevent low pH–dependent fusion of the viral membrane–endosomal membrane, which mainly blocks the release of the viral genome from the endosome to the cytoplasm and then restricts viral late entry. Taken together, our results indicate that the scorpion venom peptide Ev37 is a broad-spectrum antiviral agent with a specific molecular mechanism against viruses undergoing low pH–dependent fusion activation during entry into host cells. We conclude that Ev37 is a potential candidate for development as an antiviral drug.
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spelling pubmed-63228762020-01-04 A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles Li, Fangfang Lang, Yange Ji, Zhenglin Xia, Zhiqiang Han, Yuewen Cheng, Yuting Liu, Gaomin Sun, Fang Zhao, Yonghui Gao, Minjun Chen, Zongyun Wu, Yingliang Li, Wenxin Cao, Zhijian J Biol Chem Microbiology Viral infections still threaten human health all over the world, and many people die from viral diseases every year. However, there are no effective vaccines or drugs for preventing or managing most viral diseases. Thus, the discovery and development of broad-spectrum antiviral agents remain urgent. Here, we expressed and purified a venom peptide, Ev37, from the scorpion Euscorpiops validus in a prokaryotic system. We found that rEv37 can inhibit dengue virus type 2 (DENV-2), hepatitis C virus (HCV), Zika virus (ZIKV), and herpes simplex virus type 1 (HSV-1) infections in a dose-dependent manner at noncytotoxic concentrations, but that it has no effect on Sendai virus (SeV) and adenovirus (AdV) infections in vitro. Furthermore, rEv37 alkalized acidic organelles to prevent low pH–dependent fusion of the viral membrane–endosomal membrane, which mainly blocks the release of the viral genome from the endosome to the cytoplasm and then restricts viral late entry. Taken together, our results indicate that the scorpion venom peptide Ev37 is a broad-spectrum antiviral agent with a specific molecular mechanism against viruses undergoing low pH–dependent fusion activation during entry into host cells. We conclude that Ev37 is a potential candidate for development as an antiviral drug. American Society for Biochemistry and Molecular Biology 2019-01-04 2018-11-07 /pmc/articles/PMC6322876/ /pubmed/30404919 http://dx.doi.org/10.1074/jbc.RA118.005015 Text en © 2019 Li et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
spellingShingle Microbiology
Li, Fangfang
Lang, Yange
Ji, Zhenglin
Xia, Zhiqiang
Han, Yuewen
Cheng, Yuting
Liu, Gaomin
Sun, Fang
Zhao, Yonghui
Gao, Minjun
Chen, Zongyun
Wu, Yingliang
Li, Wenxin
Cao, Zhijian
A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles
title A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles
title_full A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles
title_fullStr A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles
title_full_unstemmed A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles
title_short A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles
title_sort scorpion venom peptide ev37 restricts viral late entry by alkalizing acidic organelles
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322876/
https://www.ncbi.nlm.nih.gov/pubmed/30404919
http://dx.doi.org/10.1074/jbc.RA118.005015
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