Imatinib and methazolamide ameliorate COVID-19-induced metabolic complications 
via elevating ACE2 enzymatic activity and inhibiting viral entry

Li, Zilun; Peng, Meixiu; Chen, Pin; Liu, Chenshu; Hu, Ao; Zhang, Yixin; Peng, Jiangyun; Liu, Jiang; Li, Yihui; Li, Wenxue; Zhu, Wei; Guan, Dongxian; Zhang, Yang; Chen, Hongyin; Li, Jiuzhou; Fan, Dongxiao; Huang, Kan; Lin, Fen; Zhang, Zefeng; Guo, Zeling; Luo, Hengli; He, Xi; Zhu, Yuanyuan; Li, Linghua; Huang, Bingding; Cai, Weikang; Gu, Lei; Lu, Yutong; Deng, Kai; Yan, Li; Chen, Sifan

doi:10.1016/j.cmet.2022.01.008

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Imatinib and methazolamide ameliorate COVID-19-induced metabolic complications via elevating ACE2 enzymatic activity and inhibiting viral entry

MPS-Authors

/persons/resource/persons262571

Gu, Lei
Epigenetics, Max Planck Institute for Heart and Lung Research, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Li, Z., Peng, M., Chen, P., Liu, C., Hu, A., Zhang, Y., et al. (2022). Imatinib and methazolamide ameliorate COVID-19-induced metabolic complications via elevating ACE2 enzymatic activity and inhibiting viral entry. CELL METABOLISM, 34(3), 424-440. doi:10.1016/j.cmet.2022.01.008.

Cite as: https://hdl.handle.net/21.11116/0000-000A-246A-7

Abstract

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.