In-silico prediction of novel drug-target complex of nsp3 of CHIKV through molecular dynamic simulation

• Main Authors: Durgesh Kumar, Mahendra Kumar Meena, Kamlesh Kumari, Rajan Patel, Abhilash Jayaraj, Prashant Singh
• Format: Article
• Language: English
• Published: Elsevier 2020-08-01
• Series: Heliyon
• Subjects: Pharmaceutical chemistry; Theoretical chemistry; Multicomponent reactions (MCRs); nsp3 of CHIKV; Docking; DFT study
• Online Access: http://www.sciencedirect.com/science/article/pii/S2405844020315632

Literature reported that nsp3 of CHIKV is an important target for the designing of drug as it involves in the replication, survival etc. Herein, about eighteen million molecules available in the ZINC database are filtered against nsp3 using RASPD. Top five hit drug molecules were then taken from the total screened molecules (6988) from ZINC database. Then, a one pot-three components reaction is designed to get the pyrazolophthalazine and its formation was studied using DFT method. Authors created a library of 200 compounds using the product obtained in the reaction and filtered against nsp3 of CHIKV based on docking using iGEMDOCK, a computational tool. Authors have studied the best molecules after applying the the Lipinski's rule of five and bioactive score. Further, the authors took the best compound i.e. CMPD178 and performed the MD simulations and tdMD simulations with nsp3 protease using AMBER18. MD trajectories were studied to collect the information about the nsp3 of CHIKV with and without screened compound and then, MM-GBSA calculations were performed to calculate change in binding free energies for the formation of complex. The aim of the work is to find the potential candidate as promising inhibitor against nsp3 of CHIKV.