Identification of JEV capsid interacting domain(s) with host protein(s): Novel target for developing anti-JEV therapeutics.

UNLABELLED: The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus. There are no approved drugs for the treatment of JEV infection.

AIM: The virus-host protein interactions are essential for viral replication and could be novel drug targets. The JEV capsid protein does not have enzymatic functions; therefore, all functions are mediated by protein-protein interactions. We wanted to develop inhibitors to prevent such interactions.

MATERIALS AND

METHODS

Our study has identified two functional domains of the capsid protein by competitive peptide binding (P2 and P7) that is crucial for JEV replication. Using pull-down and MALDI-TOF-TOF techniques, we showed that the JEV capsid protein interacts with the ANXA2 host protein via these peptide domains.

KEY FINDINGS: In the presence of P2 and P7, ANXA-2-capsid interaction in infected cells was inhibited, and concomitantly, JEV growth was reduced in the presence of both P2 and P7. Further, we docked ~55,000 molecules from the Maybridge library and identified 10 compounds that showed favourable binding to the P7 domain. From the pool of 10 compounds, we identified SPB07257, which inhibited Capsid-ANXA2 interaction, prevented JEV infection with an IC50 of 10 μM and CC50 of ⟩50 μM.

SIGNIFICANCE: Our study demonstrates a novel antiviral strategy.