Identification of potential inhibitors of coronavirus hemagglutinin-esterase using molecular docking, molecular dynamics
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ORIGINAL ARTICLE
Identification of potential inhibitors of coronavirus hemagglutinin‑esterase using molecular docking, molecular dynamics simulation and binding free energy calculation Chirag N. Patel1 · Sivakumar Prasanth Kumar2 · Himanshu A. Pandya1 · Rakesh M. Rawal2 Received: 18 June 2020 / Accepted: 18 August 2020 © Springer Nature Switzerland AG 2020
Abstract The pandemic outbreak of the Corona viral infection has become a critical global health issue. Biophysical and structural evidence shows that spike protein possesses a high binding affinity towards host angiotensin-converting enzyme 2 and viral hemagglutinin-acetylesterase (HE) glycoprotein receptor. We selected HE as a target in this study to identify potential inhibitors using a combination of various computational approaches such as molecular docking, ADMET analysis, dynamics simulations and binding free energy calculations. Virtual screening of NPACT compounds identified 3,4,5-Trihydroxy1,8-bis[(2R,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]benzo[7]annulen-6-one, Silymarin, Withanolide D, Spirosolane and Oridonin as potential HE inhibitors with better binding energy. Furthermore, molecular dynamics simulations for 100 ns time scale revealed that most of the key HE contacts were retained throughout the simulations trajectories. Binding free energy calculations using MM/PBSA approach ranked the top-five potential NPACT compounds which can act as effective HE inhibitors.
Chirag N. Patel and Sivakumar Prasanth Kumar are equal first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11030-020-10135-w) contains supplementary material, which is available to authorized users. * Rakesh M. Rawal [email protected] 1
Department of Botany, Bioinformatics, and Climate Change Impacts Management, University School of Sciences, Gujarat University, Ahmedabad 380009, India
Department of Life Sciences, University School of Sciences, Gujarat University, Ahmedabad 380009, India
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Molecular Diversity
Graphic abstract
Keywords COVID-19 virus · Angiotensin-converting enzyme 2 (ACE2) · Hemagglutinin-acetylesterase (HE) glycoprotein · Molecular docking · Molecular dynamics simulations · NPACT compounds
Introduction Coronaviruses (CoV) are a single (+)-stranded RNA containing a virus that appears as an oval-shaped envelop with spike-like protrusions [1, 2]. The first form of CoV has emerged in the Middle East which caused respiratory tract disease called the Middle East Respiratory Syndrome Coronavirus (MERS‐CoV) [3, 4]. The recent outbreak which created the global health threat is caused by a new form of CoV called CoV-2. The initial spread is traced to Hubei province, Wuhan, Republic of China. CoV infection develops asymptomatically as fever, cough, and severe shortness
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of breathing, nausea, vomiting and diarrhea symptoms [5]. The envelope of SARS-CoV composed of various types of proteins including envelope, membrane, nucleocapsid, replicase
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