10.6084/m9.figshare.9572366.v1 Durgesh Kumar Durgesh Kumar Kamlesh Kumari Kamlesh Kumari Abhilash Jayaraj Abhilash Jayaraj Prashant Singh Prashant Singh Development of a theoretical model for the inhibition of nsP3 protease of Chikungunya virus using pyranooxazoles Taylor & Francis Group 2019 Chikungunya virus nsP3 protease one-pot reaction docking MD simulation MM-GBSA and DFT 2019-08-13 07:17:48 Journal contribution https://tandf.figshare.com/articles/journal_contribution/Development_of_a_theoretical_model_for_the_inhibition_of_nsP3_protease_of_Chikungunya_virus_using_pyranooxazoles/9572366 <p>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</p><p>Chikungunya fever</p>CHIKV<p>Chikungunya virus</p>DFT<p>density functional theory</p>DS<p>Discovery Studio</p>MD<p>molecular dynamics</p>MM-GBSA<p>molecular mechanics-generalized born surface area</p>MMV<p>Molegro molecular viewer</p><p></p> <p>Chikungunya fever</p> <p>Chikungunya virus</p> <p>density functional theory</p> <p>Discovery Studio</p> <p>molecular dynamics</p> <p>molecular mechanics-generalized born surface area</p> <p>Molegro molecular viewer</p> <p>Communicated by Ramaswamy H. Sarma</p>