Computational in silico screening of Himalayan Phytochemicals Against the Oncogenic Chaperone Protein (AGR2): Exploring Nepal's Biodiversity for Accessible Cancer Therapeutics

Abstract

Anterior Gradient 2 (AGR2) is an endoplasmic reticulum molecular chaperone heavily implicated in aggressive tumor progression, metastasis, and therapeutic resistance across multiple malignancies. Intercepting its interaction pathways with small-molecule inhibitors represents a high-priority therapeutic focus. This study details a systematic, comparative in silico virtual screening of five key secondary metabolites derived from Himalayan ethnobotanical frameworks (specifically Bergenia ciliata and Picrorhiza kurroa) using AlphaFold structural configurations and the AutoDock Vina engine, accessed via the MTiOpenScreen web server. Our computational matrix reveals that 11-O-Galloyl bergenin exhibits peak binding affinity (ΔG = -8.74 kcal/mol), closely followed by foundational Bergenin (ΔG = -8.61 kcal/mol) and rigid Ellagic Acid (ΔG = -8.55 kcal/mol). Systematic literature audits across PubMed and Google Scholar databases returned zero matching citations connecting these specific ligands to AGR2 modulation, suggesting that these therapeutic pathways have not previously been reported in the literature reviewed. This work establishes a preliminary Structure-Activity Relationship (SAR) baseline intended to inform downstream in vitro experimental validation.