tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2024 Sep 18;9(1):243.
doi: 10.1038/s41392-024-01956-4. Characterization of ACTN4 as a novel antiviral target against SARS-CoV-2
Miao Zhu[SUP] #[/SUP][SUP] 1 2 [/SUP], Fang Huang[SUP] #[/SUP][SUP] 3 [/SUP], Huize Sun[SUP] #[/SUP][SUP] 1 2 [/SUP], Kunpeng Liu[SUP] 1 2 [/SUP], Zhen Chen[SUP] 1 [/SUP], Baocheng Yu[SUP] 1 2 [/SUP], Haojie Hao[SUP] 1 [/SUP], Haizhou Liu[SUP] 1 [/SUP], Shuang Ding[SUP] 1 [/SUP], Xueyan Zhang[SUP] 1 [/SUP], Lishi Liu[SUP] 1 2 [/SUP], Kui Zhang[SUP] 1 2 [/SUP], Jierao Ren[SUP] 1 2 [/SUP], Yi Liu[SUP] 3 [/SUP], Haibin Liu[SUP] 1 3 [/SUP], Chao Shan[SUP] 1 3 [/SUP], Wuxiang Guan[SUP] 4 5 [/SUP]
Affiliations
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.
. 2024 Sep 18;9(1):243.
doi: 10.1038/s41392-024-01956-4. Characterization of ACTN4 as a novel antiviral target against SARS-CoV-2
Miao Zhu[SUP] #[/SUP][SUP] 1 2 [/SUP], Fang Huang[SUP] #[/SUP][SUP] 3 [/SUP], Huize Sun[SUP] #[/SUP][SUP] 1 2 [/SUP], Kunpeng Liu[SUP] 1 2 [/SUP], Zhen Chen[SUP] 1 [/SUP], Baocheng Yu[SUP] 1 2 [/SUP], Haojie Hao[SUP] 1 [/SUP], Haizhou Liu[SUP] 1 [/SUP], Shuang Ding[SUP] 1 [/SUP], Xueyan Zhang[SUP] 1 [/SUP], Lishi Liu[SUP] 1 2 [/SUP], Kui Zhang[SUP] 1 2 [/SUP], Jierao Ren[SUP] 1 2 [/SUP], Yi Liu[SUP] 3 [/SUP], Haibin Liu[SUP] 1 3 [/SUP], Chao Shan[SUP] 1 3 [/SUP], Wuxiang Guan[SUP] 4 5 [/SUP]
Affiliations
- PMID: 39289355
- DOI: 10.1038/s41392-024-01956-4
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.