Synthesis, crystal structure elucidation, DFT analysis, drug‐likeness and ADMET evaluation and molecular docking studies of triazole derivatives: Binary inhibition of spike protein and ACE2 receptor protein of COVID‐19

Abstract

The recent incidence of terrible acute respiratory syndrome coronavirus 2 (SARS CoV‐2) has presently experienced some noteworthy mutations since its discovery in 2019 in Wuhan, China. The present research work focuses on the synthesis of three triazole derivatives (BMTPP, BMTTP, and BMTIP) and their inhibition activities against SARS‐Cov‐2 spike and ACE2 receptor proteins. The crystal structure for BMTTP was determined by the SCXRD method and optimized geometrical parameters for the three triazole derivatives were obtained by DFT calculations. HOMO‐LUMO, Global reactive descriptors [GRD], and Molecular electrostatic potential (MEP) investigations exposed that all three compounds have biological properties. The drug‐likeness ability of the synthesized compounds was examined using Molinspiration and a pre‐ADMET online Server. Further, to explore the binding nature of three synthesized compounds with SARS‐Cov‐2 spike proteins/ACE2 receptor molecular docking studies were executed. The outcomes we obtained from molecular docking simulation studies suggest that the synthesized triazole derivatives may be well utilized as curing medicines against COVID‐19. Ultimately, animal tests and precise clinical tests are required to prove the potent nature of these compounds against COVID‐19. Finally, the present outcomes must be proved to utilize in‐vitro and in‐vivo antiviral methods.

Exploring the inhibitory potential of novel piperidine-derivatives against main protease (Mpro) of SARS-CoV-2: A hybrid approach consisting of molecular docking, MD simulations and MMPBSA analysis

“…The GCRD is an essential parameter to figure out the chemical reactivity, stability, and bioactivity of compounds [52] . These parameters include ionization energy (I), electron affinity (A), chemical hardness (η), chemical potential (μ), electronegativity index (χ), electrophilicity index (ω), and softness (S) that were calculated based on the energy values of FMOs and are displayed in tabulated form (Table S10).…”

A Comprehensive Update of Anti-COVID-19 Activity of Heterocyclic Compounds

“…Murugavel et al, 4 prepared triazole derivatives and tested them as potent inhibitors of COVID-19 using in silico analyses. From these, compound 81 showed a remarkable binding affinity for the spike protein (PDB ID: 7DF4) of SARS-CoV-2 (−8.9Kcal/mol).…”

“… 3 The Beta, Delta, and Omicron variants started to emerge in Africa in May 2020, in India by October 2020, and in various other regions in November 2021, causing many concerns worldwide. 4 The coronavirus, is highly contagious in the air, can transmit from one person to another through respiratory aerosols and droplets. 5 , 6 The breathing problems caused by COVID-19 can be fatal in some cases, resulting in a global public health emergency.…”

Discovery of promising cholinesterase inhibitors for Alzheimer's disease treatment through DFT, docking, and molecular dynamics studies of eugenol derivatives

“…Molecular docking is powerful computational technique frequently used to assess the affinity of ligands toward a protein target whose three-dimensional structure is well known. [18][19][20] In other words, it evaluates the ability of ligands to match energetically and geometrically the active site of a protein. Herein, molecular docking studies were performed using AutoDock Vina 1.1.2 software [21] to assess the binding affinities and the interactions involved between a series of eugenol derivatives and Cholinesterase proteins, namely Butyrylcholinesterase (BuChE) and Acetylcholinesterase (AChE).…”