Promising inhibitors of nsp2 of CHIKV using molecular docking and temperature-dependent molecular dynamics simulations

Abstract

Infection due to the Chikungunya virus (CHIKV) has taken the life of lots of people; and researchers are working to find the vaccine or promisng drug candidates against this viral infection. In this work, the authors have designed one component reaction based on the thia-/oxa-azolidineone and created a library of 2000 molecules based on the product obtained. Further, the compounds were screened through the docking using iGemdock against the non-structural protein 2 (nsp2) of CHIKV. Molecular docking gives the binding energy (BE) or energy for the formation of the complex between the designed compound and nsp2 of CHIKV; and CMPD222 gave the lowest energy. This is based on the energy obtained from van der Waal’s interaction, hydrogen bonding and electrostatic instructions. Further, molecular dynamics simulations (MDS) of nsp2 of CHIKV with and without screened compound (222) were performed to validate the docking results and the change in free energy for the formation of the complex is −10.8327 kcal/mol. To explore the potential of CMPD222, the MDS of the CMPD222-nsp2 of CHIKV were performed at different temperatures (325, 350, 375 and 400 K) to understand the inhibition of the protease. MM-GBSA calculations were performed to determined change in entropy, change in enthalpy and change in free energy to understand the inhibition. Maximum inhibition of nsp2 of CHIKV with CMPD222 is observed at 375 K with a change in free energy of −19.3754 kcal/mol.

Communicated by Ramaswamy H. Sarma

Keywords:

• nsp2 of CHIKV
• docking
• molecular dynamics simulations
• inhibitors

Acknowledgments

Durgesh Kumar (DK) is thankful to Prof. B. Jayaram, Incharge, SCFBio, Indian Institute of Technology, Delhi, India for accessing the facilities and the training. This work is dedicated to late Dr. Vandana Oberoi, Associate Professor, Department of Chemistry, Acharya Narendra Dev College, University of Delhi.

Disclosure statement

There is no potential conflict of interest. Mahendra Kumar Meena, Durgesh Kumar and Lata Vodwal performed the experiments and did analysis of results; Indra Bahadur, Nagendera Kumar Kaushik and Rammapa Venkatesh Kumar have designed the experiments; discussed results of screening through docking and help in writing the manuscript; Kamlesh Kumari and Prashant Singh have conceived the idea; analyzed the results and concluded the results.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.