Nucleoside and non-nucleoside reverse transcriptase inhibitor drugs (NRTIs and NNRTIs) are capable of binding Chandipura virus polymerase protein (L) and inhibit virus replication

Dibyakanti Mandal; Deeksha Pandey; Debi P Sarkar; Manish Kumar

doi:10.1007/s13337-024-00883-w

Nucleoside and non-nucleoside reverse transcriptase inhibitor drugs (NRTIs and NNRTIs) are capable of binding Chandipura virus polymerase protein (L) and inhibit virus replication

Virusdisease. 2024 Sep;35(3):420-427. doi: 10.1007/s13337-024-00883-w. Epub 2024 Jul 8.

Authors

Dibyakanti Mandal¹, Deeksha Pandey², Debi P Sarkar³, Manish Kumar²

Affiliations

¹ Amity Institute of Biotechnology, Amity University, Noida, India.
² Department of Biophysics, University of Delhi, South Campus, Benito Jaurez Marg, New Delhi, 110021 India.
³ Department of Biochemistry, University of Delhi South Campus, New Delhi, India.

PMID: 39464733
PMCID: PMC11502645 (available on 2025-09-01)
DOI: 10.1007/s13337-024-00883-w

Abstract

Chandipura virus (CHPV) is an emerging pathogen of Indian subcontinent. It is a vector borne virus and belongs to Rhabdovirus family. In recent past several outbreaks reported from the states of "Maharastha", "Gujrat", "Andra Pradesh" causing more than 300 deaths of children below 15 years and case-fatality rate was more than 50%. There is no targeted drug or vaccine available against CHPV and symptomatic treatment is the option. We hypothesized that nucleoside and non-nucleoside reverse transcriptase inhibitor drugs will be able to inhibit CHPV replication because of close structural similarity of the viral polymerases within the finger, palm and thumb domains. We examined the inhibitory effects of NRTI drugs AZT, tenofovir, abacavir and NNRTI drug nevirapine on CHPV replication in Vero cells. We have performed plaque assays and western blotting to determine the levels of inhibition of virus replication. We found significant inhibition of CHPV by all these 4 drugs in the order abacavir > nevirapine > tenofovir > AZT. To gain an insight into drug mediated inhibition, we performed docking and molecular modelling of CHPV polymerase protein L bound to these drugs. Detailed methodology and a part of these results have been published in a preprint server (BioRxiv, 2022, doi: https://doi.org/10.1101/2022.03.02.482698). We summarize that abacavir, tenofovir, AZT and nevirapine are effective inhibitors of CHPV and a combination therapy may be designed to treat the disease.

Supplementary information: The online version contains supplementary material available at 10.1007/s13337-024-00883-w.

Keywords: Chandipura virus; NNRTI; NRTI; RNA polymerase.

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