Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation

Abstract

Mosquitoes are the primary vector for West Nile virus, a flavivirus. The virus’s ability to infiltrate and establish itself in increasing numbers of nations has made it a persistent threat to public health worldwide. Despite the widespread occurrence of this potentially fatal disease, no effective treatment options are currently on the market. As a result, there is an immediate need for the research and development of novel pharmaceuticals. To begin, molecular docking was performed on two possible West Nile virus target proteins using a panel of twelve natural chemicals, including Apigenin, Resveratrol, Hesperetin, Fungisterol, Lucidone, Ganoderic acid, Curcumin, Kaempferol, Cholic acid, Chlorogenic acid, Pinocembrin, and Sanguinarine. West Nile virus methyltransferase (PDB ID: 2OY0) binding affinities varied from −7.4 to −8.3 kcal/mol, whereas West Nile virus envelope glycoprotein affinities ranged from −6.2 to −8.1 kcal/mol (PDB ID: 2I69). Second, substances with larger molecular weights are less likely to be unhappy with the Lipinski rule. Hence, additional research was carried out without regard to molecular weight. In addition, compounds 01, 02, 03, 05, 06, 07, 08, 09, 10 and 11 are more soluble in water than compound 04 is. Besides, based on maximum binding affinity, best three compounds (Apigenin, Curcumin, and Ganoderic Acid) has been carried out molecular dynamic simulation (MDs) at 100 ns to determine their stability. The MDs data is also reported that these mentioned molecules are highly stable. Finally, advanced principal component analysis (PCA), dynamics cross-correlation matrices (DCCM) analysis, binding free energy and dynamic cross correlation matrix (DCCM) theoretical study is also included to established mentioned phytochemical as a potential drug candidate. Research has indicated that the aforementioned natural substances may be an effective tool in the battle against the dangerous West Nile virus. This study aims to locate a bioactive natural component that might be used as a pharmaceutical.

3D-QSAR and Molecular Dynamics Study of Isoxazole Derivatives to Identify the Structural Requirements for Farnesoid X Receptor (FXR) Agonists

“…DCCM analysis is a prominent method for analyzing the trajectory of MD simulations, with the aim of generating a matrix of cross-correlations, indicating correlations and anticorrelations between atoms during displacement or fluctuations. Correlations closer to +1 (inky blue) indicate that the residues were moving in the same direction, while correlations closer to −1 (yellowish) indicate that the residues were moving in opposite directions [ 42 ]. More yellowish blocks are shown in Figure 12 B–D, suggesting more negative correlations in the motions of the residues in the FXR-cilofexor, FXR-LY2562175, and FXR-PX20606 systems and fewer negative correlations in the motions of the residues in the FXR-GW4064 system.…”

“…The root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding analysis, and radius of gyration (Rg) were used to analyze the MD trajectory. The RMSD was used to analyze global conformational dynamics and the stabilities of proteins [ 42 ]. RMSF was used to describe the fluctuation of each amino acid residue [ 68 ].…”

Interplay of precision therapeutics and MD study: Calocybe indica's potentials against cervical cancer and its interaction with VEGF via octadecanoic acid

“…While certain nuances prompt us to consider stability parameters, the overarching narrative from MM‐GBSA underscores the pronounced binding affinity of Octadecanoic acid with VEGF. Emerging therapeutic modalities, including proteolysis‐targeting chimeras (PROTACs) and innovative nanocarriers such as exosomes and liposomes, 28 , 29 , 30 further elevate the therapeutic potential when considered in tandem with compounds like C. indica . The integration of these facets suggests a fertile ground for future therapeutic endeavours.…”

“…To represent the molecular interactions, the OPLS‐2005 force field was employed, which has been described in previous studies 24‐26 . An explicit solvent model was used, utilizing SPC molecules 27,28 . The simulation system OCTADECANOIC ACIDs enclosed in a periodic boundary salvation box with dimensions of 10 Å × 10 Å × 10 Å.…”

“… 24 , 25 , 26 An explicit solvent model was used, utilizing SPC molecules. 27 , 28 The simulation system OCTADECANOIC ACIDs enclosed in a periodic boundary salvation box with dimensions of 10 Å × 10 Å × 10 Å. Sodium ions (Na + ) were added to neutralize the system's charge, and NaCl solutions were introduced to mimic the physiological environment.…”