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Antimicrobial peptide WK-13-3D inhibits Japanese encephalitis virus infection by interacting with viral particles,
Fengxue Chai1, Takele Adugna Kassegn2, Junzheng Du1
1State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China; Key Laboratory of Veterinary Parasitology of Gansu Province, Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou, Gansu, China.
Abstract:
Despite causing fatal encephalitis and long-term neurological, cognitive, and behavioral impairments in survivors, no antiviral drugs are currently available to treat Japanese encephalitis virus (JEV) infections, highlighting the urgent need for effective therapies. Antimicrobial peptides (AMPs) exhibit broad-spectrum antibiotic activity; LL-37 is one such AMP that demonstrates a broad antiviral effect against various viruses. However, some viruses resist LL-37 and its analogues, emphasizing the importance of studying the impact of specific antimicrobial peptides on different viruses. In this study, we found that the synthetic LL-37 analogue peptide WK-13-3D has strong antiviral activity against JEV. Notably, pre-treatment or co-incubation during virus adsorption led to a noticeable reduction in infection levels in human glioblastoma (T98G) cells. Mechanistically, WK-13-3D inhibits JEV infection by directly binding to the viral particle, potentially Envelope (E) protein and preventing internalization. This peptide conferred protection against mortality in JEV-infected mice. In vivo, pre-treating JEV with WK-13-3D provided complete protection against death, compared to only 16.66% survival in the control group. Overall, these results suggest that WK-13-3D could be a promising candidate for further development as an immediate post-exposure antiviral treatment or prophylactic intervention for JEV infection.
Insights
A new peptide, WK-13-3D, shows strong antiviral activity against Japanese encephalitis virus (JEV). This peptide protects against JEV infection and mortality in both cell cultures and mice.
Area of Science:
- Virology
- Drug Discovery
- Neuroscience
Background:
- Japanese encephalitis virus (JEV) causes fatal encephalitis and neurological impairments, with no current antiviral treatments.
- Antimicrobial peptides (AMPs) like LL-37 have shown broad antiviral effects, but efficacy varies by virus.
- Understanding specific AMP-virus interactions is crucial for developing targeted therapies.
Purpose of the Study:
- To evaluate the antiviral activity of the synthetic LL-37 analogue peptide WK-13-3D against JEV.
- To investigate the mechanism of action of WK-13-3D against JEV infection.
- To assess the therapeutic potential of WK-13-3D in a JEV mouse model.
Main Methods:
- Assessed WK-13-3D antiviral activity in human glioblastoma (T98G) cells.
- Investigated peptide-virus interaction and cellular uptake inhibition.
- Evaluated in vivo efficacy and survival rates in JEV-infected mice.
Main Results:
- WK-13-3D significantly reduced JEV infection levels in T98G cells when pre-treated or co-incubated during adsorption.
- The peptide directly binds to JEV particles, potentially the Envelope (E) protein, inhibiting viral entry.
- WK-13-3D provided complete protection against mortality in JEV-infected mice, compared to 16.66% survival in controls.
Conclusions:
- The synthetic peptide WK-13-3D demonstrates potent antiviral activity against JEV.
- WK-13-3D acts by inhibiting JEV internalization into host cells.
- WK-13-3D shows promise as a potential prophylactic or post-exposure treatment for Japanese encephalitis.
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