详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

Structure of the enterovirus D68 RNA-dependent RNA polymerase in complex with NADPH implicates an inhibitor binding site in the RNA template tunnel.

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]State Key Lab of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China [2]Institute of Life Sciences, Chongqing Medical University, Chongqing, China [3]Department of Respiratory Diseases, Children's Hospital of Chongqing Medical University, Chongqing, China [4]School of Bioscience and Technology, Chengdu Medical College, Chengdu, China [5]West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China

出处：

DOI：

ISSN：

关键词： Enterovirus Enterovirus D68 RdRp NADPH Anti-enterovirus inhibitor

摘要：

Enterovirus D68 (EV-D68) is an emerging viral pathogen belonging to the Enterovirus genus of the Picornaviridae family, which is a serious threat to human health and has resulted in significant economic losses. The EV-D68 genome encodes an RNA-dependent RNA polymerase (RdRp) 3Dpol, which is central for viral genome replication and considered as a promising target for specific antiviral therapeutics. In this study, we report the crystal structures of human EV-D68 RdRp in the apo state and in complex with the inhibitor NADPH, which was selected by using a structure-based virtual screening approach. The EV-D68-RdRp-NADPH complex is the first RdRp-inhibitor structure identified in the species Enterovirus D. The inhibitor NADPH occupies the RNA template binding channel of EV-D68 RdRp with a novel binding pocket. Additionally, residues involved in the NADPH binding pocket of EV-D68 RdRp are highly conserved in RdRps of enteroviruses. Therefore, the enzyme activity of three RdRps from EV-D68, poliovirus, and enterovirus A71 is shown to decrease when titrated with NADPH separately in vitro. Furthermore, we identified that NADPH plays a pivotal role as an RdRp inhibitor instead of a chain terminator during restriction of RNA-dependent RNA replication. In the future, derivatives of NADPH may pave the way for novel inhibitors of RdRp through compound modification, providing potential antiviral agents for treating enteroviral infection and related diseases. Copyright © 2020. Published by Elsevier Inc.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2020]版：

大类 | 3 区生物学

小类 | 3 区生化与分子生物学 3 区生物物理 4 区细胞生物学

最新[2025]版：

大类 | 3 区生物学

小类 | 3 区生物物理 4 区生化与分子生物学 4 区细胞生物学

第一作者：

第一作者机构： [1]State Key Lab of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China

共同第一作者：

通讯作者：

通讯机构： [1]State Key Lab of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China [4]School of Bioscience and Technology, Chengdu Medical College, Chengdu, China [5]West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China [*1]State Key Lab of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, China.

推荐引用方式(GB/T 7714)：

APA：

MLA：

Structure of the enterovirus D68 RNA-dependent RNA polymerase in complex with NADPH implicates an inhibitor binding site in the RNA template tunnel.

文献详情

相关文献