Author:

Keywords:

Science & Technology, Physical Sciences, Technology, Chemistry, Physical, Nanoscience & Nanotechnology, Materials Science, Multidisciplinary, Physics, Atomic, Molecular & Chemical, Chemistry, Science & Technology - Other Topics, Materials Science, Physics, CURCUMIN BASED DESIGN, PYRAZOLINE ANALOGS, CARAGANA-SINICA, PROTEIN, METABOLITES, PARAMETERS, DYNAMICS, INSIGHTS, VIRUS, AMBER, Angiotensin-Converting Enzyme 2, Animals, Chlorocebus aethiops, Computer Simulation, Drug Design, Humans, Hydrophobic and Hydrophilic Interactions, Molecular Docking Simulation, Protein Binding, Receptors, Coronavirus, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Stilbenes, Vero Cells, COVID-19 Drug Treatment, 02 Physical Sciences, 03 Chemical Sciences, 34 Chemical sciences, 51 Physical sciences

Abstract:

In the search for inhibitors of COVID-19, we have targeted the interaction between the human angiotensin-converting enzyme 2 (ACE2) receptor and the spike receptor binding domain (S1-RBD) of SARS-CoV-2. Virtual screening of a library of natural compounds identified Kobophenol A as a potential inhibitor. Kobophenol A was then found to block the interaction between the ACE2 receptor and S1-RBD in vitro with an IC50 of 1.81 ± 0.04 μM and inhibit SARS-CoV-2 viral infection in cells with an EC50 of 71.6 μM. Blind docking calculations identified two potential binding sites, and molecular dynamics simulations predicted binding free energies of -19.0 ± 4.3 and -24.9 ± 6.9 kcal/mol for Kobophenol A to the spike/ACE2 interface and the ACE2 hydrophobic pocket, respectively. In summary, Kobophenol A, identified through docking studies, is the first compound that inhibits SARS-CoV-2 binding to cells through blocking S1-RBD to the host ACE2 receptor and thus may serve as a good lead compound against COVID-19.