A tripeptide (NSK) inhibits Japanese encephalitis virus infection in vitro and in vivo

Japanese encephalitis virus (JEV) is a major pathogen that can cause acute viral encephalitis in both humans and animals. Domain III of the viral envelope protein (EDIII) is involved in binding to host cell receptor(s) to facilitate virus entry. Our previous study showed that the loop3 peptide of EDIII possesses antiviral activity against JEV infection. In this paper, we demonstrate that three residues (NSK) in loop3 are responsible for the antiviral activity of loop3 peptide. In vitro experiments showed that the tripeptide NSK could inhibit JEV infection in both BHK-21 and Neuro-2A cells by inhibiting attachment of JEV to the cells, with IC50 values of 8 mu M and 6.5 mu M, respectively. In vivo experiments showed that the tripeptide could increase the survival of mice challenged with JEV to 75 % when administrated intracerebrally. Therefore, this tripeptide may serve as the basis for the development of novel antiviral agents against Japanese encephalitis virus infection.