Assessing the inhibitory potential of anti-dengue compounds against Japanese encephalitis virus RNA dependent RNA polymerase: an in silico study

Abstract

Japanese encephalitis (JE), a neurological infection of severe nature, is caused by the Japanese encephalitis virus (JEV) and is transmitted by the mosquito vector. The polymerase domain of Non-structural 5 (NS5), which is also referred to as RdRp (RNA-dependent RNA polymerase), is considered a potential therapeutic target for JEV. The present study employed molecular dynamics modelling and high-throughput virtual screening to evaluate the possible antiviral activity of anti-dengue drugs against JEV RdRp. Furthermore, a ranking was performed utilising the MM/GBSA analysis to identify the three most promising compounds. Compound ID 57409246 exhibited the highest binding affinity with the protein, as evidenced by its minimum binding free energy of −72.96 kcal/mole. In contrast, the other two compounds had minimum binding free energies of −67.57 and −59.19 kcal/mole, respectively. Upon conducting a 100 nanosecond molecular dynamics simulation to confirm the binding of the chemical complexes, it was observed that the three hits, namely 57409246, 70683874, and 44577154, exhibited a consistent and stable RMSD. Subsequently, the binding strength of the trajectory was confirmed through MM/GBSA analysis. The compounds 70683874 and 57409246 exhibited the lowest binding free energies, which were −97.58 kcal/mol and −96.38 kcal/mol, respectively. The binding free energy (ΔG Bind) values for the native ligand ATP and molecule 44577154 were −65.64 kcal/mol and −69.44 kcal/mol, respectively. Overall, compared to the native ligand ATP, all three compounds exhibited higher binding affinity. The study proposes three anti-dengue molecules as a potential remedy for JE, which can be confirmed through in vitro and in vivo investigations.

Communicated by Ramaswamy H. Sarma

Keywords:

• Japanese encephalitis
• molecular docking
• virtual high throughput screening
• molecular dynamic simulation
• anti-dengue compounds

Acknowledgments

The authors are highly thankful to Dr. Amaresh Kumar Sahoo, Indian Institute of Information Technology, Prayagraj, India for providing his kind support for giving access to Schrödinger suite software package.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.