Phytochemicals from Leucas zeylanica Targeting Main Protease of SARS-CoV-2: Chemical Profiles, Molecular Docking, and Molecular Dynamics Simulations

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a contemporary coronavirus, has impacted global economic activity and has a high transmission rate. As a result of the virus’s severe medical effects, developing effective vaccinations is vital. Plant-derived metabolites have been discovered as potential SARS-CoV-2 inhibitors. The SARS-CoV-2 main protease (Mpro) is a target for therapeutic research because of its highly conserved protein sequence. Gas chromatography–mass spectrometry (GC-MS) and molecular docking were used to screen 34 compounds identified from Leucas zeylanica for potential inhibitory activity against the SARS-CoV-2 Mpro. In addition, prime molecular mechanics–generalized Born surface area (MM-GBSA) was used to screen the compound dataset using a molecular dynamics simulation. From molecular docking analysis, 26 compounds were capable of interaction with the SARS-CoV-2 Mpro, while three compounds, namely 11-oxa-dispiro[4.0.4.1]undecan-1-ol (−5.755 kcal/mol), azetidin-2-one 3,3-dimethyl-4-(1-aminoethyl) (−5.39 kcal/mol), and lorazepam, 2TMS derivative (−5.246 kcal/mol), exhibited the highest docking scores. These three ligands were assessed by MM-GBSA, which revealed that they bind with the necessary Mpro amino acids in the catalytic groove to cause protein inhibition, including Ser144, Cys145, and His41. The molecular dynamics simulation confirmed the complex rigidity and stability of the docked ligand–Mpro complexes based on the analysis of mean radical variations, root-mean-square fluctuations, solvent-accessible surface area, radius of gyration, and hydrogen bond formation. The study of the postmolecular dynamics confirmation also confirmed that lorazepam, 11-oxa-dispiro[4.0.4.1]undecan-1-ol, and azetidin-2-one-3, 3-dimethyl-4-(1-aminoethyl) interact with similar Mpro binding pockets. The results of our computerized drug design approach may assist in the fight against SARS-CoV-2.

In Silico Evaluation of Iranian Medicinal Plant Phytoconstituents as Inhibitors against Main Protease and the Receptor-Binding Domain of SARS-CoV-2

“…However, the molecular mechanisms of how these herbal medicines interact with SARS-CoV-2 and how this virus causes COVID-19 have remained elusive. Some preliminary studies have investigated potential combinations that include the protease inhibitor lopinavir/ritonavir, which is commonly used to treat human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients, for the treatment of COVID-19-infected patients [ 13 , 14 ]. In the present study, we investigated 169 components from 82 Iranian medicinal plants as potential candidates for COVID-19 management using in silico methods (molecular docking and molecular dynamics (MD) simulation).…”

Interactions of the Receptor Binding Domain of SARS-CoV-2 Variants with hACE2: Insights from Molecular Docking Analysis and Molecular Dynamic Simulation

“…As a result, global monitoring of the continuing genomic changes in SARS-CoV-2 is critical for identifying areas linked with drug resistance and vaccine evasion in order to create successful antiviral medicines. Several drug-repositioning studies and compound evaluations have been conducted to discover novel antiviral medicines against SARS-CoV-2 utilizing experimental and theoretical/computational methodologies [ 36 , 37 , 38 ].…”

Molecular Docking and Dynamics Studies to Explore Effective Inhibitory Peptides Against the Spike Receptor Binding Domain of SARS-CoV-2

“…The simulations were run for 100 ns at constant pressure and temperature, using a Berendsen thermostat. The simulation trajectories were used to calculate root mean square deviations, root mean square fluctuations, solvent accessible surface areas, radii of gyration, and hydrogen bonds ( Adji et al, 2021 ; Dutta et al, 2021 ; Obaidullah et al, 2021 ).…”