2. Academic Validation
  3. CDK4/6 inhibitor palbociclib promotes SARS-CoV-2 cell entry by down-regulating SKP2 dependent ACE2 degradation

CDK4/6 inhibitor palbociclib promotes SARS-CoV-2 cell entry by down-regulating SKP2 dependent ACE2 degradation

  • Antiviral Res. 2023 Feb 18;105558. doi: 10.1016/j.antiviral.2023.105558.
Yingzi Xiao 1,  Ying Yan 2,  Le Chang 2,  Huimin Ji 2,  Huizhen Sun 1,  Shi Song 1,  Kaihao Feng 1,  Abudulimutailipu Nuermaimaiti 1,  Zhuoqun Lu 2,  Lunan Wang 3
Affiliations

Affiliations

  • 1 National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital / National Center of Gerontology, Beijing, PR China; National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, PR China; Beijing Engineering Research Center of Laboratory Medicine, Beijing, PR China.
  • 2 National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital / National Center of Gerontology, Beijing, PR China; Beijing Engineering Research Center of Laboratory Medicine, Beijing, PR China.
  • 3 National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital / National Center of Gerontology, Beijing, PR China; National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, PR China; Beijing Engineering Research Center of Laboratory Medicine, Beijing, PR China. Electronic address: lunan99@163.com.
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z