tetano
Editor, Senior Moderator
Antiviral Res
. 2023 Feb 18;105558.
doi: 10.1016/j.antiviral.2023.105558. Online ahead of print.
CDK4/6 inhibitor palbociclib promotes SARS-CoV-2 cell entry by down-regulating SKP2 dependent ACE2 degradation
Yingzi Xiao[SUP] 1 [/SUP], Ying Yan[SUP] 2 [/SUP], Le Chang[SUP] 2 [/SUP], Huimin Ji[SUP] 2 [/SUP], Huizhen Sun[SUP] 1 [/SUP], Shi Song[SUP] 1 [/SUP], Kaihao Feng[SUP] 1 [/SUP], Abudulimutailipu Nuermaimaiti[SUP] 1 [/SUP], Zhuoqun Lu[SUP] 2 [/SUP], Lunan Wang[SUP] 3 [/SUP]
Affiliations
Abstract
Coronavirus disease 2019 (COVID-19) outbreak has become a global pandemic. CDK4/6 inhibitor palbociclib was reported to be one of the top-scored repurposed drugs to treat COVID-19. As the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry, expression level of angiotensin-converting enzyme 2 (ACE2) is closely related to SARS-CoV-2 infection. In this study, we demonstrated that palbociclib and other methods could arrest cells in G0/G1 phase and up-regulate ACE2 mRNA and protein levels without altering its subcellular localization. Palbociclib inhibited ubiquitin-proteasome and lysosomal degradation of ACE2 through down-regulating S-phase kinase-associated protein 2 (SKP2). In addition, increased ACE2 expression induced by palbociclib and other cell cycle arresting compounds facilitated pseudotyped SARS-CoV-2 infection. This study suggested that ACE2 expression was down-regulated in proliferating cells. Cell cycle arresting compounds could increase ACE2 expression and facilitate SARS-CoV-2 cell entry, which may not be suitable therapeutic agents for the treatment of SARS-CoV-2 infection.
Keywords: ACE2; Cell cycle; Cell proliferation; Degradation; Palbociclib; SARS-CoV-2; SKP2.
. 2023 Feb 18;105558.
doi: 10.1016/j.antiviral.2023.105558. Online ahead of print.
CDK4/6 inhibitor palbociclib promotes SARS-CoV-2 cell entry by down-regulating SKP2 dependent ACE2 degradation
Yingzi Xiao[SUP] 1 [/SUP], Ying Yan[SUP] 2 [/SUP], Le Chang[SUP] 2 [/SUP], Huimin Ji[SUP] 2 [/SUP], Huizhen Sun[SUP] 1 [/SUP], Shi Song[SUP] 1 [/SUP], Kaihao Feng[SUP] 1 [/SUP], Abudulimutailipu Nuermaimaiti[SUP] 1 [/SUP], Zhuoqun Lu[SUP] 2 [/SUP], Lunan Wang[SUP] 3 [/SUP]
Affiliations
- PMID: 36806814
- DOI: 10.1016/j.antiviral.2023.105558
Abstract
Coronavirus disease 2019 (COVID-19) outbreak has become a global pandemic. CDK4/6 inhibitor palbociclib was reported to be one of the top-scored repurposed drugs to treat COVID-19. As the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry, expression level of angiotensin-converting enzyme 2 (ACE2) is closely related to SARS-CoV-2 infection. In this study, we demonstrated that palbociclib and other methods could arrest cells in G0/G1 phase and up-regulate ACE2 mRNA and protein levels without altering its subcellular localization. Palbociclib inhibited ubiquitin-proteasome and lysosomal degradation of ACE2 through down-regulating S-phase kinase-associated protein 2 (SKP2). In addition, increased ACE2 expression induced by palbociclib and other cell cycle arresting compounds facilitated pseudotyped SARS-CoV-2 infection. This study suggested that ACE2 expression was down-regulated in proliferating cells. Cell cycle arresting compounds could increase ACE2 expression and facilitate SARS-CoV-2 cell entry, which may not be suitable therapeutic agents for the treatment of SARS-CoV-2 infection.
Keywords: ACE2; Cell cycle; Cell proliferation; Degradation; Palbociclib; SARS-CoV-2; SKP2.