Systematic virtual screening in search of SARS CoV-2 inhibitors against spike glycoprotein: pharmacophore screening, molecular docking, ADMET analysis and MD simulations

The severe acute respiratory syndrome SARS‐CoV‐2 is the causative agent of COVID‐19. Preventing binding of SARS‐CoV‐2 Spike glycoprotein to human ACE2 enzyme and inhibition of MPRO enzyme are still attractive drug targets for treatment of COVID‐19 infection. Boron atom‐containing compounds show anticancer, antibacterial, antiviral, antifungal, antiparasitic, anti‐inflammatory, antituberculosis, anti‐dermatophytic and anti‐fertility activities. In the current study, the ADMET properties of ligands were calculated by the aim of SwissADME and pkCSM pharmacokinetics web tools. The results revealed that the ligands meet drug‐likeness properties. Furthermore, we have performed molecular docking study of boron containing dioxaborepine and oxadiazaborole derivatives to investigate binding properties of ligands against SARS‐CoV‐2 Spike glycoprotein/ACE2 complex and inhibition of MPRO enzyme. Through the ligands a derivative of dioxaborepine showed best binding score against SARS‐CoV‐2 Spike glycoprotein/ACE2 complex with a binding score of −8.93 kcal/mol and a oxadiazaborole derivative exhibited a binding score value of −8.36 kcal which is the best binding ligand to the MPRO enzyme binding site. The analysis of binding poses of ligands and ligand‐residue interactions of the systems revealed that dioxaborepines and oxadiazaboroles could have block binding of Spike glycoprotein to human ACE2 enzyme and could have inhibition effects on MPRO enzyme.

Section: )mentioning

confidence: 99%

Molecular Docking Studies of Boron‐Containing Compounds as Dual Inhibitors of SARS‐Cov‐2 Spike Receptor Binding Domain/ACE2 Complex and Main Protease and ADMET Investigations

Ercan,

Pir

2023

“…Recently humanity has savagely hit by COVID-19 at the dawn of this decade. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS CoV-2), [29][30][31] it has infected approximately 250 million people and has taken the life of close to 440 million lives globally as of March 4, 2022 according to WHO. [32] Hydroxychloroquine was thought to repurpose for COVID-19 treatment due to its immunomodulatory activity.…”

Section: Biological Importance Of Quinolinesmentioning

confidence: 99%

Environmentally Benign Approaches towards the Synthesis of Quinolines

Kumar

Dhameliya²,

Sharma

et al. 2022

Self Cite

Greener and sustainable synthetic strategies have been evolving as the demanding domain of organic transformations during the last decade. The division of an environmentally benign methodology to construct bioactive heterocyclic scaffolds has always been a perpetual subject of interests for medicinal and synthetic chemists. Thus, the newer and novel synthetic methodologies of quinoline have drawn the attention of synthetic organic or medicinal chemists as evident from the growing numbers of publications. The current review focuses on some of the notable synthetic methodologies carried out in the last decade with the inherent objective to attain sustainability towards the synthesis. The key aspects of the review would include to highlight sustainable and environmentally benign approaches like the solvent‐free reactions, use of alternate reaction media (e. g., water, fluorous alcohols, polyethylene glycols, and ionic liquids), and alternate modes of synthesis such as microwave‐assisted synthesis and flow reactions, nano‐catalysts, etc.

“…The molecular dynamics (MD) simulations provide the stability of ligand at the active site of protein through the study of several statistical parameters. [50][51][52]58] Next, we studied the stability of 5u at the binding site of mmpL3 using GROMACS 2020.1 for 20 ns and the results of MD Simulation of the complex of 5u with mmpL3 are graphically represented in Figure 4. The compound 5u was found to deviate with an average of 0.293 nm as evident from the plot of RMSD for ligand (RMSDÀ L, Figure 4a).…”

Section: Simulationsmentioning

confidence: 99%

Indole‐2‐carboxamides as New Anti‐Mycobacterial Agents: Design, Synthesis, Biological Evaluation and Molecular Modeling against mmpL3

Bhakhar¹,

Vaghela²,

Varakala

et al. 2022

Self Cite

Tuberculosis (TB), an airborne disease caused by Mycobacterium tuberculosis, has infected millions of people and been responsible for their deaths. Toward the anti‐TB endeavor, the synthesis of total twenty‐four indole‐2‐carboxamide derivatives as potent anti‐TB agents have been carried out using CDI‐mediated amidation. The biological evaluation against H37Rv revealed compounds 5d, 5e and 5u with MICs in the range of 3.125‐12.5 μg/mL using MABA assay. Further, compound 5u was tested against RAW 264.7 cell by MTT assay and showed 32 % growth inhibitions. The structure activity relationship of the indole‐2‐carboxamides has been established for antimycobacterial activity. The physicochemical properties and ADMET parameters of the 5d, 5e and 5u using pKCSM and SwissADME revealed their suitability as promising drug candidates. Molecular docking studies using AutoDock Vina revealed binding of 5u with the catalytic site of mmpL3 (PDB ID: 6AJG). The MD simulations of the most active compound 5u using GROMACS 2020.1 revealed its stability at the protein active site. Further optimization of indole‐2‐carboxamies may reveal the potentiation of identified anti‐mycobacterial drug candidates.