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Open AccessArticle

An Antiviral Peptide from Alopecosa nagpag Spider Targets NS2B–NS3 Protease of Flaviviruses

by Mengyao Ji 1,2,†, Tengyu Zhu 1,2,†, Meichen Xing 1,2,†, Ning Luan 1, James Mwangi 2, Xiuwen Yan 1, Guoxiang Mo 1, Mingqiang Rong 3, Bowen Li 2, Ren Lai 1,2,4,5,6,7,* and Lin Jin 2,*
1
College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China
2
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
3
The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China
4
KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
5
Sino-African Joint Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
6
Institute for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai 201203, China
7
Center for Biosafety Mega-Science, Chinese Academy of Sciences, No.44, Xiaohongshan, Wuchang District/Huangjin Industrial Park, Zhengdian Street, Jiangxia District, Wuhan 430207, Hubei, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Toxins 2019, 11(10), 584; https://doi.org/10.3390/toxins11100584
Received: 30 August 2019 / Revised: 24 September 2019 / Accepted: 8 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Animal Venoms and Their Components: Molecular Mechanisms of Action)
Flaviviruses are single-stranded RNA viruses predominantly transmitted by the widely distributed Aedes mosquitoes in nature. As important human pathogens, the geographic reach of Flaviviruses and their threats to public health are increasing, but there is currently no approved specific drug for treatment. In recent years, the development of peptide antivirals has gained much attention. Natural host defense peptides which uniquely evolved to protect the hosts have been shown to have antiviral properties. In this study, we firstly collected the venom of the Alopecosa nagpag spider from Shangri-La County, Yunnan Province. A defense peptide named Av-LCTX-An1a (Antiviral-Lycotoxin-An1a) was identified from the spider venom, and its anti-dengue serotype-2 virus (DENV2) activity was verified in vitro. Moreover, a real-time fluorescence-based protease inhibition assay showed that An1a functions as a DENV2 NS2B–NS3 protease inhibitor. Furthermore, we also found that An1a restricts zika virus (ZIKV) infection by inhibiting the ZIKV NS2B–NS3 protease. Together, our findings not only demonstrate that An1a might be a candidate for anti-flavivirus drug but also indicate that spider venom is a potential resource library rich in antiviral precursor molecules. View Full-Text
Keywords: Alopecosa nagpag; dengue virus; Zika virus; host defense peptide; NS2B–NS3 protease; Flavivirus Alopecosa nagpag; dengue virus; Zika virus; host defense peptide; NS2B–NS3 protease; Flavivirus
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MDPI and ACS Style

Ji, M.; Zhu, T.; Xing, M.; Luan, N.; Mwangi, J.; Yan, X.; Mo, G.; Rong, M.; Li, B.; Lai, R.; Jin, L. An Antiviral Peptide from Alopecosa nagpag Spider Targets NS2B–NS3 Protease of Flaviviruses. Toxins 2019, 11, 584.

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