DFT, molecular docking and molecular dynamics simulation studies on some newly introduced natural products for their potential use against SARS-CoV-2

Abstract

Throughout the history, natural products always give new paths to develop new drugs. As with many other diseases, natural compounds can be helpful in the treatment of COVID-19. SARS-CoV-2 main protease enzyme has an important role in viral replication and transcription. Therefore, inhibiting this enzyme may be helpful in the treatment of COVID-19. In this study, it is aimed to investigate eight natural compounds which have recently entered the literature, computationally for their potential use against SARS-CoV-2. For this purpose, first, density functional theory (DFT) calculations were performed on the investigated compounds, and energy minimizations, geometry optimizations, vibrational analyses, molecular electrostatic potential map calculations were carried out. After DFT calculations, geometry optimized structures were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (pdb id: 5r80) and top-scoring ligand-receptor complexes were obtained. In the next part of the study, molecular dynamics (MD) simulations were performed on the top-scoring ligand-receptor complexes to investigate the stability of the ligand-receptor complexes and the interactions between ligands and receptor in more detail. Additionally, in this part of the study, binding free energies are calculated with the use of molecular mechanics with Poisson-Boltzmann surface area (MM-PBSA) method. Results showed that, all ligand-receptor complexes remain stable during the MD simulations and most of the investigated compounds but especially two of them showed considerably high binding affinity to SARS-CoV-2 main protease. Finally, in the study, ADME (adsorption, desorption, metabolism, excretion) predictions and drug-likeness analyses were performed on the investigated compounds.

Antibacterial and Antioxidant Activities, in silico Molecular Docking, ADMET and DFT Analysis of Compounds from Roots of Cyphostemma cyphopetalum

“…Based on the energies of HOMO and LUMO of the compounds, the chemical reactivity parameters such as energy gap (ΔE = E LUMO − E HOMO ), electronegativity (χ = − ½ (E HOMO + E LUMO ), electronic chemical potential (μ = ½ (E HOMO + E LUMO ) = − χ), global chemical hardness (η = ½ (E LUMO − E HOMO ), global softness (σ = 1/2η), global electrophilicity index (ω = μ 2 /2η), nucleophilicity index (Nu = 1/ω), dipole moment, and natural atomic charges (NAC) calculations were carried out at the same level of theory. [37][38][39]…”

(2E)-2-(4-ethoxybenzylidene)-3,4-dihydro-2H-naphthalen-1-one single crystal: Synthesis, growth, crystal structure, spectral characterization, biological evaluation and binding interactions with SARS-CoV-2 main protease

“…The binding energy, number of hydrogen bond interactions, inhibition constant and interacting amino acid residues were summarized in Table 5 . The binding energy of the synthesized chalcone compound EBDN is −7.25 Kcal/mol [39] , [40] , [41] , [42] , [43] , [44] , [45] . The EBDN has shown strong four hydrogen bond (H-bond) interaction with targeted SARS-CoV-2 main protease (6yb7).…”

“…Since it's unveiling at the end of December 2019, SARS-CoV-2 has remained to spread chop-chop throughout the world. Despite the fact that the number of deaths caused by COVID-19 is rapidly increasing, an effective drug treatment other than vaccines has yet to be developed.The existing literature comprises many investigations on SARS-CoV-2 main protease and its potential inhibitors [39] , [40] , [41] , [42] , [43] , [44] , [45] .…”

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

“…Virtual screening was also performed toward other natural products such as marine products, Indian medicinal herbs, and plant products. 238 , 612 , 613 , 620 , 621 , 719 , 1048 , 1075 − 1090 …”