高等学校化学学报2026，Vol.47Issue(6)：105-114,10.DOI:10.7503/cjcu20250317
靶向猴痘A42R病毒的药物筛选和再利用:结合机制的模拟研究
Targeting Monkeypox A42R for Drug Screening and Repurposing:A Computational Study of Binding Mechanisms
摘要
Abstract
The purpose of this study is to screen potential inhibitors targeting monkeypox virus A42R protein through drug reuse strategy to solve the current lack of specific anti-monkeypox drugs.Six candidate compounds with good binding ability to A42R were screened from 9803 small molecules in the ZINC database by molecular docking,molecular dynamics simulation and MM/PBSA(molecular mechanics/Poisson-Boltzmann surface area)binding free energy calculation.Among them,ZINC000000538152 with two negative charges has the strongest binding ability(-236.3 kJ/mol).It forms multiple salt bridges,hydrogen bonds and π-cation interactions with the arginine-rich domain of the A42R protein,which significantly enhances the binding stability.In addition,although ZINC000003935130 is a neutral molecule,it achieves a sub-high binding strength(-102.7 kJ/mol)through strong van der Waals interaction,which is greater than the other three compounds with a negative charge.The conclusion shows that these six compounds are highly potential and can be reused as candidates for A42R inhibitors,because their presence blocks the binding of A42R to actin or phosphatidylinositol-(4,5)-bisphosphate(PIP2),thereby inhibiting virus spread.This study provides new ideas for the development of monkeypox virus drugs.关键词
猴痘病毒/A42R 蛋白/药物再利用/阻断机制/分子动力学Key words
Monkeypox virus/A42R protein/Drug repurposing/Blocking mechanism/Molecular dynamics分类
化学化工引用本文复制引用
范翔,刘子建,贾梦珂,艾洪奇..靶向猴痘A42R病毒的药物筛选和再利用:结合机制的模拟研究[J].高等学校化学学报,2026,47(6):105-114,10.基金项目
山东省自然科学基金(批准号:ZR2022MB073)资助.Supported by the Shandong Provincial Natural Science Foundation,China(No.ZR2022MB073). （批准号:ZR2022MB073）
