%0 Journal Article %A Kumar, Durgesh %A Kumari, Kamlesh %A Jayaraj, Abhilash %A Singh, Prashant %D 2019 %T Development of a theoretical model for the inhibition of nsP3 protease of Chikungunya virus using pyranooxazoles %U https://tandf.figshare.com/articles/journal_contribution/Development_of_a_theoretical_model_for_the_inhibition_of_nsP3_protease_of_Chikungunya_virus_using_pyranooxazoles/9572366 %R 10.6084/m9.figshare.9572366.v1 %2 https://tandf.figshare.com/ndownloader/files/17206415 %K Chikungunya virus %K nsP3 protease %K one-pot reaction %K docking %K MD simulation %K MM-GBSA and DFT %X
Chikungunya virus (CHIKV) causes Chikungunya fever (CHIKF) and till date no effective medicine for its cure is available in market. Different research groups find various possible interactions between small molecules and non-structural proteins, viz. nsP3, one of the most important viral elements in CHIKV. In this work, authors have studied the interactions of nsP3 protease of CHIKV with pyranooxazoles. Initially, a one-pot three-component reaction was designed using oxazolidine-2,4-dione, benzaldehyde and cyanoethylacetate to get a proposed biological active molecule, i.e. based on pyranooxazoles. The mechanism for the synthesis of the product based on pyranooxazole was studied through density functional theory (DFT) using Gaussian. Then, a library of the obtained pyranooxazole was created through computational tools by varying the substituents. Further, virtual screening of the designed library of pyranooxazoles (200 compounds) against nsP3 protease of CHIKV was performed. Herein, CMPD 104 showed strongest binding affinity toward the targeted nsP3 protease of CHIKV, based on the least binding energy obtained from docking. Based on docking results, the pharmacological, toxicity, biological score and Lipinski’s filters were studied. Further, DFT studies of top five compounds were done using Gaussian. Molecular dynamics (MD) simulation of nsP3 protease of CHIKV with and without 104 was performed using AMBER18 utilizing ff14SB force field in three steps (minimization, equilibration and production). This work is emphasized to designing of one-pot three-component synthesis and to develop a theoretical model to inhibit the nsP3 protease of CHIKV. AbbreviationsCHIKF
Chikungunya fever
CHIKVChikungunya virus
DFTdensity functional theory
DSDiscovery Studio
MDmolecular dynamics
MM-GBSAmolecular mechanics-generalized born surface area
MMVMolegro molecular viewer
Chikungunya fever
Chikungunya virus
density functional theory
Discovery Studio
molecular dynamics
molecular mechanics-generalized born surface area
Molegro molecular viewer
Communicated by Ramaswamy H. Sarma
%I Taylor & Francis