tetano
Editor, Senior Moderator
ACS Infect Dis
. 2024 Feb 22.
doi: 10.1021/acsinfecdis.3c00418. Online ahead of print. Ubiquitin Ligase Parkin Regulates the Stability of SARS-CoV-2 Main Protease and Suppresses Viral Replication
Li Zhou[SUP] 1 [/SUP], Ruochuan Liu[SUP] 1 [/SUP], Heather Pathak[SUP] 2 [/SUP], Xiaoyu Wang[SUP] 1 [/SUP], Geon H Jeong[SUP] 1 [/SUP], Pratima Kumari[SUP] 2 [/SUP], Mukesh Kumar[SUP] 2 [/SUP], Jun Yin[SUP] 1 [/SUP]
Affiliations
The highly infectious coronavirus SARS-CoV-2 relies on the viral main protease (M[SUP]pro[/SUP], also known as 3CLpro or Nsp5) to proteolytically process the polyproteins encoded by the viral genome for the release of functional units in the host cells to initiate viral replication. M[SUP]pro[/SUP] also interacts with host proteins of the innate immune pathways, such as IRF3 and STAT1, to suppress their activities and facilitate virus survival and proliferation. To identify the host mechanism for regulating M[SUP]pro[/SUP], we screened various classes of E3 ubiquitin ligases and found that Parkin of the RING-between-RING family can induce the ubiquitination and degradation of M[SUP]pro[/SUP] in the cell. Furthermore, when the cells undergo mitophagy, the PINK1 kinase activates Parkin and enhances the ubiquitination of M[SUP]pro[/SUP]. We also found that elevated expression of Parkin in the cells significantly decreased the replication of SARS-CoV-2 virus. Interestingly, SARS-CoV-2 infection downregulates Parkin expression in the mouse lung tissues compared to healthy controls. These results suggest an antiviral role of Parkin as a ubiquitin ligase targeting M[SUP]pro[/SUP] and the potential for exploiting the virus-host interaction mediated by Parkin to treat SARS-CoV-2 infection.
Keywords: E3 ubiquitin ligase; Parkin; SARS-CoV-2; main protease; mitophagy.
. 2024 Feb 22.
doi: 10.1021/acsinfecdis.3c00418. Online ahead of print. Ubiquitin Ligase Parkin Regulates the Stability of SARS-CoV-2 Main Protease and Suppresses Viral Replication
Li Zhou[SUP] 1 [/SUP], Ruochuan Liu[SUP] 1 [/SUP], Heather Pathak[SUP] 2 [/SUP], Xiaoyu Wang[SUP] 1 [/SUP], Geon H Jeong[SUP] 1 [/SUP], Pratima Kumari[SUP] 2 [/SUP], Mukesh Kumar[SUP] 2 [/SUP], Jun Yin[SUP] 1 [/SUP]
Affiliations
- PMID: 38386664
- DOI: 10.1021/acsinfecdis.3c00418
The highly infectious coronavirus SARS-CoV-2 relies on the viral main protease (M[SUP]pro[/SUP], also known as 3CLpro or Nsp5) to proteolytically process the polyproteins encoded by the viral genome for the release of functional units in the host cells to initiate viral replication. M[SUP]pro[/SUP] also interacts with host proteins of the innate immune pathways, such as IRF3 and STAT1, to suppress their activities and facilitate virus survival and proliferation. To identify the host mechanism for regulating M[SUP]pro[/SUP], we screened various classes of E3 ubiquitin ligases and found that Parkin of the RING-between-RING family can induce the ubiquitination and degradation of M[SUP]pro[/SUP] in the cell. Furthermore, when the cells undergo mitophagy, the PINK1 kinase activates Parkin and enhances the ubiquitination of M[SUP]pro[/SUP]. We also found that elevated expression of Parkin in the cells significantly decreased the replication of SARS-CoV-2 virus. Interestingly, SARS-CoV-2 infection downregulates Parkin expression in the mouse lung tissues compared to healthy controls. These results suggest an antiviral role of Parkin as a ubiquitin ligase targeting M[SUP]pro[/SUP] and the potential for exploiting the virus-host interaction mediated by Parkin to treat SARS-CoV-2 infection.
Keywords: E3 ubiquitin ligase; Parkin; SARS-CoV-2; main protease; mitophagy.