Phytochemicals as potential inhibitors for COVID-19 revealed by molecular docking, molecular dynamic simulation and DFT studies

Abstract

The COVID-19 pandemic outbreak demands the designing of potential drugs as there is no specific treatment available. Thanks to their safety and effectiveness, phytochemicals have been used to treat various diseases, including antiviral therapeutics. Molecular docking is a simple, quick, and effective way to screen a variety of molecules for structure-based drug design. Here, we investigate molecular docking experiments on compounds present in plant species, Cocculus hirsutus and Rhodiola rosea and show their potential for the treatment of COVID-19. Almost all the components showed higher binding affinity than the built-in ligand, and those with significantly higher binding affinity were explored further. Molecular mechanics-based generalized born surface area calculations were used to re-rank the top candidates, rhodionidin and cocsoline, and their stability in association with viral protease was confirmed. Density functional theory was used for detailed investigations of the geometries, and electrical properties of rhodionidin and cocsoline. Using the frontier molecular orbitals method, the charge transfer within the molecule was calculated. Chemical reactivity and intermolecular interactions were studied using molecular electrostatic potential maps. These in silico discoveries will simulate the identification of powerful COVID-19 inhibitors, and similar research is likely to make a significant contribution to antiviral drug discovery.

Synthesis, Characterization, In Silico DFT, Molecular Docking, and Dynamics Simulation Studies of Phenylhydrazono Phenoxyquinolones for Their Hypoglycemic Efficacy

“…The energies of FMOs and chemical reactivity descriptors based on FMOs for synthesized phenylhydrazono phenoxyquinoline derivatives ( 5a – 5x ) were calculated utilizing the DFT method. ,, Previously reported protocols were followed for carrying out the DFT calculations. ,, The B3LYP/DEF2-SVP level of theory and the ORCA 5.0.4 program were employed for the execution of all the DFT calculations. − Input and output files were generated on orca-enhanced Avogadro software. , The chemical reactivity descriptors were calculated with previously reported equations from Koopmans’ theory. , …”

“… 48 , 49 The chemical reactivity descriptors were calculated with previously reported equations from Koopmans’ theory. 50 , 51 …”

“…48,49 The chemical reactivity descriptors were calculated with previously reported equations from Koopmans' theory. 50,51 Molecular Docking Study. Target Protein Retrieval and Preparation.…”

Exploration of limonoids for their broad spectrum antiviral potential via DFT, molecular docking and molecular dynamics simulation approach

“…The frontier molecular orbitals (FMO) as well as chemical and global reactivity descriptors for the selected limonoids were calculated using the DFT method (Miar et al 2021). Reactivity descriptors such as dipole moment (DM), ionization potential (IP), electron affinity (EA), global hardness (η), chemical potential (μ), electronegativity (χ), electrophilicity (ω) were calculated as per the equations of Koopmans' theory (Patial and Cannoo 2021;Elkaeed et al 2022;Puthanveedu and Muraleedharan 2022). The B3LYP functional and def2-SVP basis set for DFT computation using Orca 4.2.1 software (Neese 2012;Kausar and Nayeem 2018).…”

A Guide to In Silico Drug Design

“…In QM setting this is found by understanding the change in potential energy surface (PES) between states. This approach extends on how ligands interact with targets to understand how the PES is modified or overcome by generation or outcompeting of bonds [ 400 , 418 , 419 , 420 , 421 ]. Extending from PES alone, application analytical tools related to the properties of the wavefunction can be used to describe, modify and improve ligands.…”