Designed thiazolidines: an arsenal for the inhibition of nsP3 of CHIKV using molecular docking and MD simulations

• Published in: Journal of biomolecular structure & dynamics Vol. 40; no. 4; pp. 1607 - 1616
• Main Authors: Meena, Mahendra Kumar, Kumar, Durgesh, Jayaraj, Abhilash, Kumar, Ajay, Kumari, Kamlesh, Katata-Seru, L. M., Bahadur, Indra, Kumar, Vinod, Sherawat, Anjali, Singh, Prashant
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.03.2022
• Subjects: Animals; Chikungunya virus - chemistry; Humans; inhibition; MCRs; molecular docking; Molecular Docking Simulation; Molecular Dynamics Simulation; molecular dynamics simulations; nsp3 of CHIKV; Thiazolidines; Viral Nonstructural Proteins - chemistry; Virus Replication; molecular dynamics simulations; inhibition; MCRs; molecular docking; nsp3 of CHIKV
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2020.1832918

Chikungunya virus (CHIKV) belongs to the alpha virus and it's infection in humans causes fever, known as chikungunya fever (CHIKF). It is a sudden onset of fever and may affect humans badly. The mode of transmission to human occurs due to the biting of the mosquitoes. Till date, thousands of humans are affected from this virus throughout the world. As on date, no promising medicine or vaccine is available in the market to cure from this viral infection. Therefore, there is a need of promising candidate against the nsp3 of CHIKV. In the present work, a library of the compounds are designed based on the product obtained in a multi-component reaction. Then, the designed compounds are filtered based on binding energy against the nsp3 of CHIKV obtained using molecular docking. Further, to understand the interaction of nsp3 of CHIKV and screened compound, CMPD474, the molecular dynamics (MD) simulations at different temperatures, that is, 300, 325, 350, 375, and 400 K is performed. The binding or the formation of the complex is studied through different trajectories obtained from MD simulations. The accurate information for the binding energy is determined by performing MM-GBSA calculations and the best inhibition was observed at 300 K as the change in free energy for the formation of the complex is -7.0523 kcal/mol. Communicated by Ramaswamy H. Sarma