Virtual Screening and Molecular Dynamics Simulation Targeting the ATP Domain of African Swine Fever Virus Type II DNA Topoisomerase
文献类型： 外文期刊
作者： Zhao, Rui 1 ; Hou, Lezi 3 ; Tesfagaber, Weldu 2 ; Song, Linfei 2 ; Zhang, Zhenjiang 2 ; Li, Fang 2 ; Bu, Zhigao 2 ; Zhao, Dongming 1 ;
作者机构： 1.Xinjiang Agr Univ, Coll Vet Med, Urumqi 830052, Peoples R China
2.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Natl African Swine Fever Para Reference Lab,Natl H, Harbin 150069, Peoples R China
3.Henan Agr Univ, Coll Vet Med, Zhengzhou 450046, Peoples R China
关键词： ASFV; type II DNA topoisomerase; ATPase domain; small molecule inhibitors; virtual screening
期刊名称：VIRUSES-BASEL （ 影响因子：3.5； 五年影响因子：3.7 ）
ISSN：
年卷期： 2025 年 17 卷 5 期
页码：
收录情况： SCI
摘要： African Swine Fever Virus (ASFV) Topo II ATPase domain, resistant to conventional inhibitors (e.g., ICRF-187) due to M18/W19 steric clashes, was targeted via hierarchical virtual screening (Schr & ouml;dinger) of the Chembridge library combined with MM/GBSA calculations. Five ligands (10012949, 40242484, 46712145, 15880207, and 33688815) showed high affinity, with 46712145 adopting symmetrical pi-pi stacking, hydrogen bonds, and alkyl interactions to bypass steric hindrance. Molecular dynamics simulations (100 ns) revealed ligand-induced flexibility, evidenced by elevated RMSD/Rg values versus the free protein. DCCM analysis highlighted enhanced anti-correlated motions between GHKL motifs and sensor domains in chain B/C, suggesting stabilization of a non-catalytic conformation to inhibit ATP hydrolysis. Free energy landscape (FEL) analysis showed 46712145 occupying a broad, shallow energy basin, enabling conformational adaptability, contrasting the narrow deep well of the free protein. This study proposes a symmetric ligand design strategy and conformational capture mechanism to block ATPase activity. Compound 46712145 demonstrates stable binding and dynamic regulation, providing a novel lead scaffold for anti-ASFV drug development. These findings establish a structural framework for combating ASFV through targeted ATPase inhibition.
- 相关文献
作者其他论文 更多>>
-
Integration of digital phenotyping, GWAS, and transcriptomic analysis revealed a key gene for bud size in tea plant (Camellia sinensis)
作者：Zhang, Shuran;Chen, Si;Fu, Zhilu;Li, Fang;Chen, Qiyu;Ma, Jianqiang;Chen, Liang;Chen, Jiedan;Chen, Yuanquan
关键词：
-
Transcriptomic and morphologic vascular aberrations underlying FCDIIb etiology
作者：Fang, Chuantao;Sun, Licheng;Lu, Yujia;Guo, Jingjing;Mei, Xinyu;Qi, Dashi;Fang, Chuantao;Zhang, Xiaodan;Yang, Lin;Wang, Min;Tan, Yanfeng;Zhang, Jinsen;Liu, Guoping;Zhang, Fayong;Zhao, Rui;Qi, Dashi;Fang, Chuantao;Zhang, Xiaodan;Yang, Lin;Wang, Min;Tan, Yanfeng;Zhang, Jinsen;Liu, Guoping;Zhang, Fayong;Zhao, Rui;Qi, Dashi;Fang, Chuantao;Zhang, Xiaodan;Yang, Lin;Wang, Min;Tan, Yanfeng;Zhang, Jinsen;Liu, Guoping;Zhang, Fayong;Zhao, Rui;Qi, Dashi;Fang, Chuantao;Liu, Yi;Xiao, Jianbo;Gao, Xin;Zhu, Li;Ren, Maozhi;Ma, Shaojie;Zhao, Rui;Zhao, Rui
关键词：
-
Age-Related Water Use Pattern of the Introduced Species Atriplex canescens Was Influenced by Root Distribution in Desert
作者：Zhou, Hai;He, Zhibin;Liu, Bing;Ren, Heng;Yang, Qiyue;Kang, Jianjun;Wang, Shuai;Zhao, Wenzhi;Feng, Xiangyan;Li, Fang
关键词：
-
Physiological differences between Mo17 and B73 maize inbred lines under salt stress
作者：Zhang, Shujie;Wen, Xinyue;Zhou, Guangshun;Li, Fang;Han, Yanlai;Wang, Yi;Han, Yanlai;Wang, Yi;Wen, Xinyue;Cui, Pengjuan
关键词：Oxidative damage; plant growth; salt stress;
Zea mays L; ion balance -
Glycosyl structure guided design, synthesis and biological accessment of chitin degrading enzyme inhibitors with insecticidal activity
作者：Ai, Yin;Zhang, Yanjun;Li, Fang;Zhou, Xingyue;Dong, Yanhong;Zhang, Jianjun;Chen, Wei;Yang, Qing;Yang, Qing
关键词：Insecticide; C -glycoside; Inhibitor; Molecular dynamics simulations; Multitarget
-
Establishment of an immunoperoxidase monolayer assay for the detection of African swine fever virus antibodies
作者：Yin, Li;Wang, Wan;Liu, Fan;Zhang, Zhenjiang;Tesfagaber, Weldu;Liu, Renqiang;Li, Fang;Bu, Zhigao;Zhu, Yuanmao;Zhao, Dongming;Zhao, Dongming
关键词：African swine fever virus; Cell-adapted strain; Wild boar kidney cells; IPMA; Antibody; Serological diagnosis
-
Susceptibility of Ferret and Cat to Porcine Deltacoronavirus: Evidence of Infection in Ferrets But Not Cats
作者：Meng, Shuhuai;Liu, Renqiang;Shuai, Lei;Guo, Huijuan;Dang, Yijing;Bu, Zhigao;Wen, Zhiyuan;Zhang, Hao;Hu, Guangli;Cao, Yongchang;Bu, Zhigao
关键词：cats; ferrets; interspecies transmission; porcine deltacoronavirus (PDCoV)
