ArticleCell metabolism2022
Imatinib and methazolamide ameliorate COVID-19-induced metabolic complications via elevating ACE2 enzymatic activity and inhibiting viral entry.
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Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Imatinib treatment improves hyperglycaemic dysregulation in severe COVID-19: a secondary analysis of blood biomarkers in a randomised controlled trial.Critical care (London, England) · 2024Trial
- Sexual dimorphism of COVID-19 inspires drug repositioning and host-targeting immunotherapy for viral pneumonia.Signal transduction and targeted therapy · 2026Article
- A synthetic angiotensin II/ACE2-based hormone shunt controlling experimental hypertension.Nature communications · 2026Article
- The mechanisms underlying COVID-19 induced insulin resistance: a narrative review.Frontiers in endocrinology · 2026Review
- Natural Fatty Acids as Dual ACE2-Inflammatory Modulators: Integrated Computational Framework for Pandemic Preparedness.International journal of molecular sciences · 2025Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Modeling mammalian hibernation to improve organ cold preservation: Using the intestine as an example.Cell research · 2025Article
- Pharmacological inhibition of hypoxia induced acidosis employing a CAIX inhibitor sensitizes gemcitabine resistant PDAC cells.Scientific reports · 2025Article
- Calbindin 2 as a Novel Biomarker and Therapeutic Target for Abdominal Aortic Aneurysm: Integrative Analysis of Human Proteomes and Genetics.Journal of the American Heart Association · 2025Article
- Carbonic anhydrase inhibitors prevent presymptomatic capillary flow disturbances in a model of cerebral amyloidosis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Angiotensin-converting enzyme 2 and hepatic SARS-CoV-2 infection: Regulation, association, and therapeutic implications.World journal of gastroenterology · 2025Article
- Epithelial DPP4 promotes Ang II-driven renal fibrosis by targeting ACE2 activity in the renin-angiotensin system.International journal of biological sciences · 2025Article
- Food-Derived Up-Regulators and Activators of Angiotensin Converting Enzyme 2: A Review.Journal of agricultural and food chemistry · 2024Review
- FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection.Signal transduction and targeted therapy · 2024Article
- Medium-Dose Formoterol Attenuated Abdominal Aortic Aneurysm Induced by EPO via β2AR/cAMP/SIRT1 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Current remarks and future directions on the interactions between metabolic dysfunction-associated fatty liver disease and COVID-19.World journal of gastroenterology · 2024Article
- Article
- Longitudinal plasma proteomics reveals biomarkers of alveolar-capillary barrier disruption in critically ill COVID-19 patients.Nature communications · 2024Article
- Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects.Frontiers in cellular and infection microbiology · 2024Review
- Butyrate Protects against SARS-CoV-2-Induced Tissue Damage in Golden Hamsters.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
31 authors at 11 institutions in 3 countries.
Zilun LiDivision of Vascular Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China. Electronic address: lizilun@mail.sysu.edu.cn.
Meixiu PengNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Pin ChenNational Supercomputer Center in Guangzhou, School of Computer Science and Engineering, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China.
Chenshu LiuDivision of Vascular Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Ao HuInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Yixin ZhangInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Jiangyun PengGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China; Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
Jiang LiuGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
Yihui LiGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China; Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
Wenxue LiGuangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong 510440, China.
Wei ZhuGuangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong 510440, China.
Dongxian GuanDivision of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Yang ZhangSchool of Public Health, Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
Hongyin ChenSchool of Public Health, Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
Jiuzhou LiSchool of Public Health, Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
Dongxiao FanDivision of Vascular Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Kan HuangDivision of Vascular Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Fen LinGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China; Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
Zefeng ZhangGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China; Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
Zeling GuoNational-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Hengli LuoGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China; Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
Xi HeGuangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510060, China.
Yuanyuan ZhuGuangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510060, China.
Linghua LiGuangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510060, China.
Bingding HuangCollege of Big Data and Internet, Shenzhen Technology University, Shenzhen, Guangdong 518118, China.
Weikang CaiDepartment of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, NY 11568, USA.
Lei GuMax Planck Institute for Heart and Lung Research and Cardiopulmonary Institute (CPI), Bad Nauheim 61231, Germany.
Yutong LuNational Supercomputer Center in Guangzhou, School of Computer Science and Engineering, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China.
Kai DengInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China; Department of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China. Electronic address: dengkai6@mail.sysu.edu.cn.
Li YanDepartment of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China. Electronic address: hfxyl@163.com.
Sifan ChenGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China; Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China. Electronic address: chensf26@mail.sysu.edu.cn.
Sun Yat-sen University · CNSun Yat-sen Memorial Hospital · CNThe First Affiliated Hospital, Sun Yat-sen University · CNGuangzhou Center for Disease Control and Prevention · CNGuangzhou Eighth People's Hospital · CNNational Supercomputing Center in Shenzhen · CNGuangzhou Medical University · CNHarvard University · USMax Planck Institute for Heart and Lung Research · DENew York Institute of Technology · USShenzhen Technology University · CN
Funding
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4MNICHD NIH HHS P50 HD105351
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.
Indexed as
COVID-19 Drug TreatmentAngiotensin-Converting Enzyme 2AnimalsCells, CulturedChlorocebus aethiopsCOVID-19Down-RegulationHEK293 CellsHumansHuman Umbilical Vein Endothelial CellsImatinib MesylateMaleMetabolic DiseasesMethazolamideMiceMice, Inbred C57BLAngiotensin-Converting Enzyme 2Imatinib MesylateMethazolamideACE2COVID-19enzymatic activatorharpagosideimatinibmetabolic complicationmethazolamideSARS-CoV-2
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