Integrated in silico Identification and Molecular Dynamics Validation of Potential Inhibitors Targeting Nav1.7 channel
Abstract
Silent myocardial ischemia (SMI) is defined as the lack of pain during ischemia and is the voltage-gated sodium channel (Nav1.7) has been implicated in the development of nociceptive deficits associated with small fibre neuropathy (SMI). The goal of this study was to use molecular modelling techniques to evaluate Epigallocatechin Gallate (EGCG) as a possible modulator of Nav1.7 via molecular docking analysis, molecular dynamics simulations (300 ns MD) and comparison to other natural products (Curcumin, Resveratrol, Capsaicin, 6Gingerol) using pharmacokinetic and toxicity predictors. Under our longitudinal assessment, the sustained binding energy of EGCG (-9.5 kcal/mol) was significantly higher than that of any other ligand. The results of MD studies on the physical characteristics of the EGCG-Nav1.7 complex revealed that the sustained 120 ns binding of EGCG to a novel and distinct corner-region binding pocket of Nav1.7 provides a potential allosteric mechanism to modulate Nav1.7 activity. The ADMET analysis showed moderate absorption and low O-availability of EGCG and ProTox-II predictions indicate minimal cardiotoxicity and possible nephrotoxicity associated with EGCG. Together, these data suggest that EGCG is a potential lead compound for targeting Nav1.7-mediated nociceptive dysfunction associated with SMI; warranting further drug development and experimental validation more common with individuals with diabetes.
How strong is the evidence?
Evidence Hub reads this as a preprint, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Noninvasive and Point-of-Care Surface-Enhanced Raman Scattering (SERS)-Based Breathalyzer for Mass Screening of Coronavirus Disease 2019 (COVID-19) under 5 min
- De Novo Transcriptome Analysis and Detection of Antimicrobial Peptides of the American Cockroach Periplaneta americana (Linnaeus)
- Molecular Characterization and Expression Profiling of Tomato GRF Transcription Factor Family Genes in Response to Abiotic Stresses and Phytohormones
- Assembly of Tight Junction Strands: Claudin-10b and Claudin-3 Form Homo Tetrameric Building Blocks that Polymerise in a Channel-Independent Manner
- Update of the Pompe variant database for the prediction of clinical phenotypes: Novel disease‐associated variants, common sequence variants, and results from newborn screening
- Machine Learning-Based SERS Chemical Space for Two-Way Prediction of Structures and Spectra of Untrained Molecules
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.