Characterization of ACTN4 as a novel antiviral target against SARS-CoV-2  

作　　者：Miao Zhu Fang Huang Huize Sun Kunpeng Liu Zhen Chen Baocheng Yu Haojie Hao Haizhou Liu Shuang Ding Xueyan Zhang Lishi Liu Kui Zhang Jierao Ren Yi Liu Haibin Liu Chao Shan Wuxiang Guan 

机构地区：[1]Center for Emerging Infectious Diseases,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,Hubei,430071,China [2]University of Chinese Academy of Sciences,Beijing,100049,China [3]Hubei Jiangxia Laboratory,Wuhan,Hubei,430200,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第10期4600-4613,共14页信号转导与靶向治疗（英文）

基　　金：National Natural Science Foundation of China[31970168];Hubei Science and Technology Major Project[2021ACB004];Key R&D Program of Hubei Province[2021BCD004];Hubei Central Leading Local Science and Technology Special Project[2022BGE245].

摘　　要：The various mutations in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pose a substantial challenge in mitigating the viral infectivity.The identification of novel host factors influencing SARS-CoV-2 replication holds potential for discovering new targets for broad-spectrum antiviral drugs that can combat future viral mutations.In this study,potential host factors regulated by SARS-CoV-2 infection were screened through different high-throughput sequencing techniques and further identified in cells.Subsequent analysis and experiments showed that the reduction of m6A modification level on ACTN4(Alpha-actinin-4)mRNA leads to a decrease in mRNA stability and translation efficiency,ultimately inhibiting ACTN4 expression.In addition,ACTN4 was demonstrated to target nsp12 for binding and characterized as a competitor for SARS-CoV-2 RNA and the RNA-dependent RNA polymerase complex,thereby impeding viral replication.Furthermore,two ACTN4 agonists,YS-49 and demethyl-coclaurine,were found to dose-dependently inhibit SARS-CoV-2 infection in both Huh7 cells and K18-hACE2 transgenic mice.Collectively,this study unveils the pivotal role of ACTN4 in SARS-CoV-2 infection,offering novel insights into the intricate interplay between the virus and host cells,and reveals two potential candidates for future anti-SARS-CoV-2 drug development.

关 键 词：DRUGS URINE holds 

分 类 号：R373[医药卫生—病原生物学]