ABSTRACT

Introduction

Chandipura virus (CHPV) is a vesiculovirus that is a member of Rhabdviridae and is an encephalitic pathogen responsible for numerous epidemics in Central and Western India. The virus affects the brain and central nervous system mainly in children under 15 age of years, leading to neurological dysfunctions. Vectors that include sand flies, mosquitoes, and ticks are the main culprits in the transmission of CHPV. Five structural proteins (N, P, M, G, and L) encode the viral genome. The nucleocapsid protein N (N protein) encapsulates the viral genomic RNA in an RNase-resistant state, which plays a crucial role in the viral life cycle. Currently, no effective vaccine or therapeutics are available to treat the viral infection, and therefore efficient interventions are urgently needed.

Methods

The repurposing of drugs is one of the best possible ways to controlCHPV infections in India and other parts of the world. In this study, we used a structure-based virtual screening approach by using FDA-approved drugs against the nucleocapsid protein of CHPV. The docking process identified a few drug candidates, which showed potent binding affinity towards the N protein. We used the Schrödinger Desmond v3.0 module; to compute the relative binding energies of ligands, we used the premier mm-GBSA module.

Results

Based on a short molecular dynamics simulation and prime MM-GBSA analysis, we identified Adrabetadex, Hydroxypropyl betadex, Beta-1,2,3,4,6-penta-O-Galloyl-D-Glucopyranose, thio-maltohexaose, and Indium-III pentetreotide as potent drug candidates for CHPV.

Conclusion

Our computational results provide suggestions for in vitro and in vivo testing of these drugs against CHPV.