Discovery of plant-based phytochemical as effective antivirals that target the non-structural protein C of the Nipah virus through computational methods

Abstract

Nipah Virus (NiV) belongs to the Paramyxoviridae family and was first identified during an outbreak in Malaysia. Some initial symptoms include mild fever, headache and sore throat, which could escalate to respiratory illness and brain inflammation. The mortality rate of NiV infection can range from 40% to 75%, which is quite high. This is mainly due to the lack of efficient drugs and vaccines. In most instances, NiV is transmitted from animals to humans. Non-Structural Proteins (C, V and W) of the Nipah virus impede the host immune response by obstructive the JAK/STAT pathway. However, Non-Structural Proteins – C (NSP-C) plays a vital role in NiV pathogenesis, which includes IFN antagonist activity and viral RNA production. In the present study, the full-length structure of NiV-NSP-C was predicted using computational modelling, and the stability of the structure was analysed using 200 ns molecular dynamic (MD) simulation. Further, the structure-based virtual screening identified five potent phytochemicals (PubChem CID: 9896047, 5885, 117678, 14887603 and 5461026) with better binding affinity against NiV-NSP-C. DFT studies clearly showed that the phytochemicals had higher chemical reactivity, and the complex MD simulation depicted that the identified inhibitors exhibited stable binding with NiV-NSP-C. Furthermore, experimental validation of these identified phytochemicals would likely control the infection of NiV.

Communicated by Ramaswamy H. Sarma

Keywords:

• Nipah virus
• non-structural protein C
• phytochemicals
• virtual screening
• MD simulation

Acknowledgements

KS thankfully acknowledges DST-SERB CRG for providing financial support in the form of research projects (No: EMR/2017/002841 and No: CVD/2020/000604) and the Central University of Punjab for the Research Seed Money (CUPB/Acad./2022/1194, Dated 19.05.2022) to conduct the study. The authors are grateful to the management of SASTRA Deemed University for providing all the necessary facilities. The authors thankfully acknowledge the high-performance computational facility in the School of Computing at SASTRA Deemed University for providing computational resources to complete the simulation studies. MS is thankful for the Senior Research Fellow grant funding from ICMR-SRF (No. Fellowship/96/2022-ECD-II, IRIS ID No.2021-11346/F96).

Disclosure statement

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