Computational studies on potential new anti-Covid-19 agents with a multi-target mode of action

Journal of King Saud University: Science

Mukesh K. Raval¹  Mohammad Azam¹  Ashish K. Sarangi¹  Azaj Ansari²  Mohnad Abdalla³  Kim Jong-Doo⁴  Sarika Verma⁴  Kuldeep Dhama⁵  Pranab K. Mohapatra⁵  Ranjan K. Mohapatra⁶  Lina Perekhoda⁷  Saud I. Al-Resayes⁸  Veronique Seidel⁹  Oval Yadav^1,10 

[1] Corresponding authors.;Buddhist Culture College, Dongguk University, Gyeongju-si, Gyeongsangbuk-do 780-714, South Korea;Department of Chemistry, C. V. Raman Global University, Bidyanagar, Mahura, Janla, Bhubaneswar, Odisha 752054, India;Department of Chemistry, Central University of Haryana, Mahendergarh, Haryana 123031, India;Department of Chemistry, College of Science, King Saud University, PO BOX 2455, Riyadh 11451, Saudi Arabia;Department of Chemistry, Government College of Engineering, Keonjhar, Odisha 758002, India;Department of Chemistry, School of Applied Sciences, Centurion University of Technology and Management, Odisha, India;Department of Medicinal Chemistry, National University of Pharmacy, Pushkinska Str. 53, Kharkiv 61002, Ukraine;Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly-243122, Uttar Pradesh, India;Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Shandong Province 250012, PR China;

关键词: Molecular electrostatic potential;    Frontiers molecular orbital;    Natural bond orbital;    Molecular docking;    Molecular dynamics;    Pharmacokinetics;   

DOI  :  

来源: DOAJ

【 摘 要 】

A compound that could inhibit multiple targets associated with SARS-CoV-2 infection would prove to be a drug of choice against the virus. Human receptor-ACE2, receptor binding domain (RBD) of SARS-CoV-2 S-protein, Papain-like protein of SARS-CoV-2 (PLpro), reverse transcriptase of SARS-CoV-2 (RdRp) were chosen for in silico study. A set of previously synthesized compounds (1–5) were docked into the active sites of the targets. Based on the docking score, ligand efficiency, binding free energy, and dissociation constants for a definite conformational position of the ligand, inhibitory potentials of the compounds were measured. The stability of the protein–ligand (P-L) complex was validated in silico by using molecular dynamics simulations using the YASARA suit. Moreover, the pharmacokinetic properties, FMO and NBO analysis were performed for ranking the potentiality of the compounds as drug. The geometry optimizations and electronic structures were investigated using DFT. As per the study, compound-5 has the best binding affinity against all four targets. Moreover, compounds 1, 3 and 5 are less toxic and can be considered for oral consumption.

【 授权许可】

Unknown