首页|Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein

Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein

扫码查看
原文链接
  • NETL
  • NSTL
  • 万方数据
The nucleocapsid protein(NP)plays a crucial role in SARS-CoV-2 replication and is the most abundant structural protein with a long half-life.Despite its vital role in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)assembly and host inflammatory response,it remains an unex-plored target for drug development.In this study,we identified a small-molecule compound(ciclopirox)that promotes NP degradation using an FDA-approved library and a drug-screening cell model.Ciclopir-ox significantly inhibited SARS-CoV-2 replication both in vitro and in vivo by inducing NP degradation.Ciclopirox induced abnormal NP aggregation through indirect interaction,leading to the formation of condensates with higher viscosity and lower mobility.These condensates were subsequently degraded via the autophagy-lysosomal pathway,ultimately resulting in a shortened NP half-life and reduced NP expression.Our results suggest that NP is a potential drug target,and that ciclopirox holds substantial promise for further development to combat SARS-CoV-2 replication.

SARS-CoV-2Nucleocapsid proteinViral replicationCiclopiroxAbnormal aggregationProtein degradationAutophagy-lysosomeDrug target

Xiafei Wei、Yuzheng Zhou、Xiaotong Shen、Lujie Fan、Donglan Liu、Xiang Gao、Jian Zhou、Yezi Wu、Yunfei Li、Wei Feng、Zheng Zhang

展开 >

Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,Southern University of Science and Technology,Shenzhen 518112,China

Guangzhou Laboratory,Guangzhou Medical University,Guangzhou 511495,China

State Key Laboratory of Respiratory Disease,National Clinical Research Center for Respiratory Disease,Guangzhou Institute of Respiratory Health,the First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510120,China

Shenzhen Science and Technology Program,ChinaNational Key Research and Development Program of ChinaShenzhen Science and Technology Program,ChinaNational Science Fund for Distinguished Young Scholars,ChinaGuangdong Basic and Applied Basic Research Foundation,ChinaGuangdong Science and Technology Plan Project,construction of highlevel biosafety laboratories,China

JCYJ202205301632060152021YFA0910900JCYJ20220818103017036820250222023A15151100332021B1212030010

2024

10.1016/j.apsb.2024.03.009

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(6)
  • 51