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.
Keywords: Angiotensin-converting enzyme 2 (ACE2); COVID-19 virus; Hemagglutinin-acetylesterase (HE) glycoprotein; Molecular docking; Molecular dynamics simulations; NPACT compounds.
【저자키워드】 molecular docking, molecular dynamics simulations, Angiotensin-converting enzyme 2 (ACE2), COVID-19 virus, Hemagglutinin-acetylesterase (HE) glycoprotein, NPACT compounds., 【초록키워드】 COVID-19, viral infection, pandemic, molecular docking, Virtual screening, molecular dynamics, molecular dynamics simulations, binding free energy, angiotensin-converting enzyme 2, inhibitors, binding affinity, Free energy calculation, Spike protein, binding energy, Molecular dynamics simulation, free energy, Free energy calculations, Health, Viral, Corona, outbreak, COVID-19 virus, target, glycoprotein, receptor, inhibitor, Critical, compounds, Angiotensin-converting enzyme, MM/PBSA, Combination, oridonin, Analysis, angiotensin, Contact, Trajectories, enzyme, Compound, Host, approach, effective, silymarin, withanolide, structural evidence, selected, identify, retained, computational approach, 【제목키워드】 coronavirus, binding free energy, Molecular dynamics simulation, Hemagglutinin-esterase, inhibitor, identification,