Journal
CELL METABOLISM
Volume 34, Issue 3, Pages 424-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2022.01.008
Keywords
-
Categories
Funding
- Guangdong Science and Technology Department [2020B1212060018, 2020B1212030004]
- Project of Educational Commission of Guangdong Province of China [2020KZDXZ1215]
Ask authors/readers for more resources
The study indicates that impairment of the ACE2 pathway is a key factor in the metabolic complications caused by COVID-19. Through screening and experiments, the researchers identified imatinib, methazolamide, and harpagoside as compounds that can directly activate ACE2. These compounds can improve metabolic disturbances and inhibit viral entry.
Coronavirus disease 2019 (COVID-19) represents a systemic disease that may cause severe metabolic complications in multiple tissues including liver, kidney, and cardiovascular system. However, the underlying mechanisms and optimal treatment remain elusive. Our study shows that impairment of ACE2 pathway is a key factor linking virus infection to its secondary metabolic sequelae. By using structure-based high-throughput virtual screening and connectivity map database, followed with experimental validations, we identify imatinib, methazolamide, and harpagoside as direct enzymatic activators of ACE2. Imatinib and methazolamide remarkably improve metabolic perturbations in vivo in an ACE2-dependent manner under the insulin-resistant state and SARS-CoV-2-infected state. Moreover, viral entry is directly inhibited by these three compounds due to allosteric inhibition of ACE2 binding to spike protein on SARS-CoV-2. Taken together, our study shows that enzymatic activation of ACE2 via imatinib, methazolamide, or harpagoside may be a conceptually new strategy to treat metabolic sequelae of COVID-19.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available