Interactions between antihyperglycemic drugs and the renin-angiotensin system: Putative roles in COVID-19. A mini-review

Nakhleh, Afif; Shehadeh, Naim

doi:10.1016/j.dsx.2020.04.040

Cited by 20 publications

(26 citation statements)

References 46 publications

(49 reference statements)

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“…For example, recent publications highlighted the significance of the two coronavirus receptor proteins, angiotensin converting enzyme 2 (ACE2) and dipeptidyl peptidase-4 (DPP4), also highlighting their dual physiologic effects as transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology and glucose homeostasis [71]. This opens the door to consider glucose-lowering agents such as the DPP4 inhibitors as tools to intervene in the interaction of COVD-19 and dysglycemic states [72].…”

Section: Discussionmentioning

confidence: 99%

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

et al. 2020

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An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection.

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Section: Discussionmentioning

confidence: 99%

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

et al. 2020

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“…Among other antidiabetic drugs, metformin and glyburide have been shown to be protective in animal models of acute lung injury through anti-inflammatory and antioxidant action, and inhibitory action on neutrophil migration. Whether these drugs or the newer class of SGLT-2 inhibitors can intervene in the ACE2 or renin-Ang II axis is also worth studying (Nakhleh and Shehadeh, 2020).…”

Section: Other Antidiabetics-mentioning

confidence: 99%

Should ACE2 be given a chance in COVID-19 therapeutics: A semi-systematic review of strategies enhancing ACE2

Kaur

Acharya

Mondal

et al. 2020

European Journal of Pharmacology

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The severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has resulted in almost 28 million cases of COVID-19 (Corona virus disease-2019) and more than 900000 deaths worldwide since December 2019. In the absence of effective antiviral therapy and vaccine, treatment of COVID-19 is largely symptomatic. By making use of its spike (S) protein, the virus binds to its primary human cell receptor, angiotensin converting enzyme 2 (ACE2) which is present in the pulmonary epithelial cells as well as other organs. SARS-CoV-2 may cause a downregulation of ACE2. ACE2 plays a protective role in the pulmonary system through its Mas-receptor and alamandine-MrgD-TGR7 pathways. Loss of this protective effect could be a major component of COVID-19 pathogenesis. An attractive strategy in SARS-CoV-2 therapeutics would be to augment ACE2 either directly by supplementation or indirectly through drugs which increase its levels or stimulate its downstream players. In this semi-systematic review, we have analysed the pathophysiological interplay between ACE and ACE2 in the cardiopulmonary system, the modulation of these two proteins by SARS-CoV-2, and potential therapeutic avenues targeting ACE-Ang II and ACE2-Ang (1–7) axes, that can be utilized against COVID-19 disease progression.

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“…Indeed, ACEi/ARBs act upregulating the receptor for entry of the virus into host pneumocytes. However, Metformin does not interfere with ACE2, and it is not clear how it could act on patients' outcome [38,39]. To date, 20 clinical trials involve metformin as potential treatment of patients with virus diseases.…”

Section: Antiviral Proprieties Of Existing Drugs Targeting Sars-cov-2mentioning

confidence: 99%

A protein interaction map identifies existing drugs targeting SARS-CoV-2

Cava

Bertoli

Castiglioni

2020

BMC Pharmacol Toxicol

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Background: Severe acute respiratory syndrome coronavirus (SARS-CoV-2), an emerging Betacoronavirus, is the causative agent of COVID-19. Angiotensin converting enzyme 2 (ACE2), being the main cell receptor of SARS-CoV-2, plays a role in the entry of the virus into the cell. Currently, there are neither specific antiviral drugs for the treatment or preventive drugs such as vaccines. Methods: We proposed a bioinformatics analysis to test in silico existing drugs as a fast way to identify an efficient therapy. We performed a differential expression analysis in order to identify differentially expressed genes in COVID-19 patients correlated with ACE-2 and we explored their direct relations with a network approach integrating also drug-gene interactions. The drugs with a central role in the network were also investigated with a molecular docking analysis. Results: We found 825 differentially expressed genes correlated with ACE2. The protein-protein interactions among differentially expressed genes identified a network of 474 genes and 1130 interactions. Conclusions: The integration of drug-gene interactions in the network and molecular docking analysis allows us to obtain several drugs with antiviral activity that, alone or in combination with other treatment options, could be considered as therapeutic approaches against COVID-19.

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Interactions between antihyperglycemic drugs and the renin-angiotensin system: Putative roles in COVID-19. A mini-review

Cited by 20 publications

References 46 publications

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

Should ACE2 be given a chance in COVID-19 therapeutics: A semi-systematic review of strategies enhancing ACE2

A protein interaction map identifies existing drugs targeting SARS-CoV-2

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