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

Li, Zilun; Peng, Mingying; Chen, Pin; Liu, Chenshu; Hu, Anbin; Zhang, Yixin; Peng, Jiangyun; Jiang, Liu; Li, Yihui; Li, Wenxue; Zhu, Wei; Guan, Dongxian; Chen, Hongyin; Li, Jiuzhou; Fan, Dongxiao; Huang, Kan; Lin, Fan-Li; Zhang, Zefeng; Guo, Zhiqiang; Luo, Hengli; He, Xiaoyun; Zhu, Yuan‐Yuan; Li, Linghua; Huang, Bingding; Cai, Weikang; Gu, Ling; Lu, Yutong; Deng, Kai; Yan, Li; Chen, Sifan

doi:10.1016/j.cmet.2022.01.008

Cited by 40 publications

(34 citation statements)

References 82 publications

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“…Our study shows that SARS-CoV-2 Spike not only binds to ACE2 to mediate virus entry but also down-regulated the expression of ACE2, indicating that the downregulation of ACE2 potentially links COVID-19 its imbalance of RAS.ACE2 downregulation has also been observed in some other viral infections, such as influenza and SARS-CoV 24 , 25 . A recent study also found that SARS-CoV-2 infection down-regulated ACE2 expression, and found that ACE2 links COVID-19 to its metabolic complications, while ACE2 activators Imatinib and methazolamide improve metabolic disorders under SARS-CoV-2 infection 26 . However, these studies do not explain the molecular mechanism of ACE2 downregulation.…”

Section: Discussionmentioning

confidence: 89%

Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection

Gao¹,

Zhang²,

Gou³

et al. 2022

Journal of Infection

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Section: Discussionmentioning

confidence: 89%

Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection

Gao¹,

Zhang²,

Gou³

et al. 2022

Journal of Infection

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“…In conclusion, the COVID-19 pandemic continues, and new variants of SARS-CoV-2, such as Omicron BA.1 and BA.2, are spreading more rapidly and aggressively. Since MAFLD is considered a growing chronic pandemic affecting a quarter of the global adult population, we need to pay more attention to COVID-19 patients with MAFLD and develop new therapeutic strategies, such as imatinib and methazolamide treatment [151], to improve metabolic complications caused by COVID-19. Moreover, we need to establish a long-term follow-up program to monitor the prognosis and incidence of liver cancer in these patients.…”

Section: Discussionmentioning

confidence: 99%

“…Mechanistically, recent studies have indicated that ACE2 plays an important role in maintaining metabolic homeostasis. SARS-CoV-2 infection impairs ACE2 expression, which in turn induces metabolic abnormalities [151]. This metabolic imbalance caused by ACE2 impairment may promote MAFLD progression in COVID-19 patients.…”

Section: Dysregulation Of Hepatic Lipid Metabolismmentioning

confidence: 99%

COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD

Chen¹,

Chen²

2022

Int. J. Biol. Sci.

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COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world's adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.

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“…ACE2 is known to be a receptor of SARS-CoV-2 and inhibition of it has been suggested as a promising strategy for COVID-19 treatment [ 51 ]. However, a recent study has unveiled a novel role of ACE2 in maintaining systemic metabolic homeostasis beyond its role in viral entry [ 52 ]. Notably, this study demonstrated that impaired ACE2 pathway might be a key player in SARS-CoV-2 related metabolic disorders, and identified imatinib, methazolamide and harpagoside as direct enzymatic activators of ACE2 by a high-throughput compound screening [ 52 ].…”

Section: Drugs Interfering With the Entry Of Sars-cov-2 Into Suscepti...mentioning

confidence: 99%

Revisiting potential value of antitumor drugs in the treatment of COVID-19

Zheng

Zeng

et al. 2022

Cell Biosci

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Since an outbreak started in China in 2019, coronavirus disease 2019 (COVID-19) has rapidly become a worldwide epidemic with high contagiousness and caused mass mortalities of infected cases around the world. Currently, available treatments for COVID-19, including supportive care, respiratory support and antiviral therapy, have shown limited efficacy. Thus, more effective therapeutic modalities are highly warranted. Drug repurposing, as an efficient strategy to explore a potential broader scope of the application of approved drugs beyond their original indications, accelerates the process of discovering safe and effective agents for a given disease. Since the outbreak of COVID-19 pandemic, drug repurposing strategy has been widely used to discover potential antiviral agents, and some of these drugs have advanced into clinical trials. Antitumor drugs compromise a vast variety of compounds and exhibit extensive mechanism of action, showing promising properties in drug repurposing. In this review, we revisit the potential value of antitumor drugs in the treatment of COVID-19 and systematically discuss their possible underlying mechanisms of the antiviral actions.

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

Cited by 40 publications

References 82 publications

Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection

Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection

COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD

Revisiting potential value of antitumor drugs in the treatment of COVID-19

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