Identification of potential inhibitors of coronavirus hemagglutinin-esterase using molecular docking, molecular dynamics simulation and binding free energy calculation

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-Trihydroxy-1,8-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.

Severe acute respiratory syndrome coronavirus 2 ORF3a induces the expression of ACE2 in oral and pulmonary epithelial cells and the food supplement Vita Deyun® diminishes this effect

“…To the best of our knowledge, there are currently no clinical reports that involve the use of silymarin against COVID-19; however, there are studies that suggest its potential use to combat this disease, as mentioned below. Taking into account the biophysical and structural evidence that spike proteins possess high binding affinity toward host ACE2 and the viral hemagglutinin esterase (HE) glycoprotein receptor, Patel et al ( 49 ) used a combination of various computational approaches to identify potential inhibitors of HE by employing the naturally occurring plant-based anticancer compound-activity-target database ( http://crdd.osdd.net/raghava/npact/ ). Subsequently, the best-scoring molecules were validated using molecular dynamics simulations and the authors identified silymarin (among other compounds) as a potential HE inhibitor with improved binding energy.…”

Biomolecular interactions with nanoparticles: applications for coronavirus disease 2019

“…Therefore, SR-B1 could also potentially be a target for therapeutic designs. Patel et al have also suggested HE as a target ( 36 ) to inhibit the virus invasion mechanism.…”

Identification of the Potential Hits for Hindering Interaction of SARS-CoV-2 Main Protease (M pro ) from the Pool of Antiviral Phytochemicals utilizing Molecular Docking and Molecular Dynamics (MD) Simulations

“…[25]. YASARA Structure (academic license) was employed for the docking experiment which comprised of water removal, the addition of polar hydrogens, steepest descent method was also used for the energy minimization [12].…”

“…The X-ray diffracted structure was fetched from Protein databank (PDB ID:6LU7; 2.16 Å resolution) which contains the single chain of 306 amino acids and co-crystal ligand N3 (N-[(5-methylisoxazol-3- [25]. YASARA Structure (academic license) was employed for the docking experiment which comprised of water removal, the addition of polar hydrogens, steepest descent method was also used for the energy minimization [12].…”

“…All the spices of the virus are branched based on genome variations and serological reaction in 7 groups namely 229E (Alpha Coronavirus), NL63 (Alpha Coronavirus), OC43 (Beta Coronavirus), HKU1 (Beta Coronavirus), MERS-CoV (Beta Coronavirus), SARS-CoV (Beta Coronavirus) and SARS-CoV-2 (Beta Coronavirus) [10]. The virus is genetically linked to the previous SARS-CoV 2003 epidemic called SARS-CoV-2 on 11 February this year by the International Committee on Virus Taxonomy (ICTV) [11] [12].…”