Abstract
(1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes ( 1 – 7 ), phenolics ( 8 – 11 ), and flavonoids ( 12 – 17 ) were isolated from Euphorbia dendroides and computationally screened against the receptor-binding domain (RBD) of the SARS-CoV-2 Omicron variant. As a first step, molecular docking calculations were performed for all investigated compounds. Promising compounds were subjected to molecular dynamics simulations (MD) for 200 ns, in addition to molecular mechanics Poisson-Boltzmann surface area calculations (MM/PBSA) to determine binding energy. (3) Results: MM/PBSA binding energy calculations showed that compound 14 (quercetin-3- O -β-D-glucuronopyranoside) and compound 15 (quercetin-3- O -glucuronide 6″- O -methyl ester) exhibited strong inhibition of Omicron, with Δ G binding of -41.0 and -32.4 kcal/mol, respectively. Finally, drug likeness evaluations based on Lipinski’s rule of five also showed that the discovered compounds exhibited good oral bioavailability. (4) Conclusions: It is foreseeable that these results provide a novel intellectual contribution in light of the decreasing prevalence of SARS-CoV-2 B.1.1.529 and could be a good addition to the therapeutic protocol.
Keywords: Euphorbia dendroides; SARS-CoV-2 Omicron; molecular docking; molecular dynamics.
【저자키워드】 molecular docking, molecular dynamics., SARS-CoV-2 Omicron, Euphorbia dendroides, 【초록키워드】 COVID-19, SARS-CoV-2, coronavirus, protocol, variant, molecular docking, quercetin, flavonoids, molecular dynamics, omicron, molecular dynamics simulations, inhibitors, binding energy, Molecular dynamics simulation, Spread, Prevalence, Receptor-binding domain, outbreak, RBD, therapeutic, Awareness, B.1.1.529, molecular, binding, compounds, Molecular mechanics, MM/PBSA, protocols, surface area, natural, Compound, oral bioavailability, FIVE, glucuronide, new SARS-CoV-2, performed, addition, investigated, raised, screened, exhibited, determine, contribute, the receptor-binding domain, Euphorbia, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, spike, Simulation, the RBD, Conducting, Euphorbia,