Developing new drugs that activate the protective arm of the renin–angiotensin system as a potential treatment for respiratory failure in COVID-19 patients

Latil, Mathilde; Camelo, Serge; Veillet, Stanislas; Lafont, René; Dilda, Pierre J.

doi:10.1016/j.drudis.2021.02.010

Cited by 22 publications

(28 citation statements)

References 65 publications

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“… 23 In another approach, cyclodextrin (CD)‐sACE2 inclusion has been suggested for the treatment of this infection. 24 Various compounds of aerosolized sACE2 to be directly inhaled into the lungs, intravenous infusion of sACE2, and ophthalmic and nasal drops made from CD‐sACE2 inclusion compounds have been suggested for the treatment of COVID‐19. 25 …”

Section: Resultsmentioning

confidence: 99%

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COVID‐19 and renin angiotensin aldosterone system: Pathogenesis and therapy

Babajani

Kakavand

Mohammadi

et al. 2021

Health Science Reports

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Aims The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) binds to the ACE2 component of the renin‐angiotensin aldosterone system (RAAS) and infects the human cells. The aims of the present review were to look at the role and alteration of the RAAS components in SARS‐CoV‐2 infection, therapeutic approaches, and clinical trials in this field. Methods We surveyed the literature (PubMed, Web of Science, and Scopus) till August 18, 2021, and 59 published papers regarding the components of the RAAS and their role and alterations in SARS‐CoV‐2 infection along with various COVID‐19 therapies based on the RASS components were included in the study. Results ACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor inhibitors are agents that significantly enhance the ACE2 and Ang‐(1‐7) levels, which can be suggestive for their role as therapeutics against SARS‐CoV‐2 infection. Beta‐adrenergic blockers, which negatively regulate renin release from juxtaglomerular cells, and vitamin D, as a regulator of the RAAS and renin expression, are proposed therapeutics in the treatment of COVID‐19. Some antihyperglycemic agents could be potentially protective against COVID‐19‐induced lung injury. Also, the inhibition of the Janus kinase/signal transducer and activator of the transcription pathway as a potential treatment for COVID‐19 has been suggested. Finally, resveratrol, an antioxidant that can suppress Ang II, has been suggested as an adjunct to other therapies. Conclusion Regarding the suggested potential therapies for COVID‐19, there are many clinical trials whose results might change the treatment strategies of SARS‐CoV‐2 infection. So, the results of well‐organized clinical trials on the efficacy and safety of the mentioned agents in the treatment of COVID‐19 will be useful in the management and therapy of the disease.

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Section: Resultsmentioning

confidence: 99%

“…Intravenous infusion of cyclic Ang‐(1–7), a more resistant form of Ang‐(1–7) to enzymatic hydrolysis, has had long‐term vasorelaxant effects in animal studies. 24 Six clinical trials related to the evaluation of Ang‐(1–7) infusion in patients with COVID‐19 are demonstrated in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

COVID‐19 and renin angiotensin aldosterone system: Pathogenesis and therapy

Babajani

Kakavand

Mohammadi

et al. 2021

Health Science Reports

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“…Part 2 is a Phase 3 pivotal randomized study to provide further evidence of the safety and efficacy of BIO101 after 28 days of double-blind dosing. BIO101 is the investigational new drug that activates the Mas1 through the protective arm of the renin-angiotensin system (RAS) [176,181].…”

Section: Covid-19mentioning

confidence: 99%

20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

et al. 2021

Self Cite

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There is growing interest in the pharmaceutical and medical applications of 20-hydroxyecdysone (20E), a polyhydroxylated steroid which naturally occurs in low but very significant amounts in invertebrates, where it has hormonal roles, and in certain plant species, where it is believed to contribute to the deterrence of invertebrate predators. Studies in vivo and in vitro have revealed beneficial effects in mammals: anabolic, hypolipidemic, anti-diabetic, anti-inflammatory, hepatoprotective, etc. The possible mode of action in mammals has been determined recently, with the main mechanism involving the activation of the Mas1 receptor, a key component of the renin–angiotensin system, which would explain many of the pleiotropic effects observed in the different animal models. Processes have been developed to produce large amounts of pharmaceutical grade 20E, and regulatory preclinical studies have assessed its lack of toxicity. The effects of 20E have been evaluated in early stage clinical trials in healthy volunteers and in patients for the treatment of neuromuscular, cardio-metabolic or respiratory diseases. The prospects and limitations of developing 20E as a drug are discussed, including the requirement for a better evaluation of its safety and pharmacological profile and for developing a production process compliant with pharmaceutical standards.

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“…Thus, appropriate ACE2 activity might be decisive in preventing immune-induced damage and ensuring tissue repair [ 16 ]. Taking all that into account, the scientific community is testing ACE inhibitors, ACE-2 agonists and Mas or AT2 receptor activators, among others [ 17 , 18 ], in hospitalised patients. It would also be of interest to study the potential therapeutic possibilities of ACE2 metabolites, including angiotensin (1-7), des-Arg (9)-bradykinin, apelin and dynorphin [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity

Gómez‐Zorita

Milton-Laskíbar

García-Arellano

et al. 2021

IJMS

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The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

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Developing new drugs that activate the protective arm of the renin–angiotensin system as a potential treatment for respiratory failure in COVID-19 patients

Cited by 22 publications

References 65 publications

COVID‐19 and renin angiotensin aldosterone system: Pathogenesis and therapy

COVID‐19 and renin angiotensin aldosterone system: Pathogenesis and therapy

20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity

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