Abstract
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.
Highlights
Flaviviruses are important human pathogens predominantly transmitted by the widely distributedAedes mosquitoes in nature
We found that An1a significantly inhibited the replication of dengue virus-2 (DENV2) (Figure 2B)
The results indicated that An1a may inhibit DENV2 replication and particle production by interacting with the NS2B–NS3 protease
Summary
Flaviviruses are important human pathogens predominantly transmitted by the widely distributedAedes mosquitoes in nature. Dengue virus (DENV), Japanese encephalitis (JEV), West. DENV is an emerging global epidemic, and its infection causes various clinical symptoms including dengue fever and dengue hemorrhagic fever [1]. The epidemic potential of ZIKV likely increased with its emergence in Pacific, Americas and Asia [3,4]. ZIKV can be classified into the African lineage, and the Asian lineage and the latter is the recent epidemic strain [5,6,7]. Recent studies have shown that ZIKV can cause severe neurological symptoms and can establish persistent infection in body fluids. Though safe and effective vaccines for JEV are available, currently, no effective vaccines or antiviral drugs have been approved for DENV and ZIKV
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