scholarly journals The Two-Way Switch Role of ACE2 in the Treatment of Novel Coronavirus Pneumonia and Underlying Comorbidities

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 142
Author(s):  
Xiao Cong Pang ◽  
Han Xu Zhang ◽  
Zhi Zhang ◽  
Suguro Rinkiko ◽  
Yi Min Cui ◽  
...  
Keyword(s):  
Hot Spot ◽  
Renin Angiotensin System ◽  
Potential Effect ◽  
Host Cells ◽  
Pharmacological Intervention ◽  
Lung Failure ◽  
Membrane Bound ◽  
Novel Coronavirus ◽  
Viral Target

December 2019 saw the emergence of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has spread across the globe. The high infectivity and ongoing mortality of SARS-CoV-2 emphasize the demand of drug discovery. Angiotensin-converting enzyme II (ACE2) is the functional receptor for SARS-CoV-2 entry into host cells. ACE2 exists as a membrane-bound protein on major viral target pulmonary epithelial cells, and its peptidase domain (PD) interacts SARS-CoV-2 spike protein with higher affinity. Therefore, targeting ACE2 is an important pharmacological intervention for a SARS-CoV-2 infection. In this review, we described the two-way switch role of ACE2 in the treatment of novel coronavirus pneumonia and underlying comorbidities, and discussed the potential effect of the ACE inhibitor and angiotensin receptor blocker on a hypertension patient with the SARS-CoV-2 infection. In addition, we analyzed the S-protein-binding site on ACE2 and suggested that blocking hot spot-31 and hot spot-353 on ACE2 could be a therapeutic strategy for preventing the spread of SARS-CoV-2. Besides, the recombinant ACE2 protein could be another potential treatment option for SARS-CoV-2 induced acute severe lung failure. This review could provide beneficial information for the development of anti-SARS-CoV-2 agents via targeting ACE2 and the clinical usage of renin-angiotensin system (RAS) drugs for novel coronavirus pneumonia treatment.

scholarly journals Moderate Intensity Aerobic Exercise Potential Favorable Effect Against COVID-19: The Role of Renin-Angiotensin System and Immunomodulatory Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Hamid Arazi ◽  
Akram Falahati ◽  
Katsuhiko Suzuki
Keyword(s):  
Physical Exercise ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Potential Effect ◽  
Moderate Intensity ◽  
Favorable Effect ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

The coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus (CoV) named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the angiotensin converting enzyme 2 (ACE2) is the cellular receptor of SARS-CoV-2, it has a strong interaction with the renin angiotensin system (RAS). Experimental studies have shown that the higher levels of ACE2 or increasing ACE2/ACE1 ratio improve COVID-19 outcomes through lowering inflammation and death. Aerobic moderate intensity physical exercise fights off infections by two mechanisms, the inhibition of ACE/Ang II/AT1-R pathway and the stimulation of ACE2/Ang-(1–7)/MasR axis. Exercise can also activate the anti-inflammatory response so that it can be a potential therapeutic strategy against COVID-19. Here, we summarize and focus the relation among COVID-19, RAS, and immune system and describe the potential effect of aerobic moderate intensity physical exercise against CoV as a useful complementary tool for providing immune protection against SARS-CoV-2 virus infection, which is a novel intervention that requires further investigation.

scholarly journals Hypertension, a Moving Target in COVID-19

2021 ◽  
Vol 128 (7) ◽  
pp. 1062-1079
Author(s):  
Carmine Savoia ◽  
Massimo Volpe ◽  
Reinhold Kreutz
Keyword(s):  
Global Health ◽  
Angiotensin Receptor Blockers ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
High Rate ◽  
Direct Role ◽  
Pressure Lowering ◽  
Ras Blockers

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associates with a considerable high rate of mortality and represents currently the most important concern in global health. The risk of more severe clinical manifestation of COVID-19 is higher in males and steeply raised with age but also increased by the presence of chronic comorbidities. Among the latter, early reports suggested that arterial hypertension associates with higher susceptibility to SARS-CoV-2 infection, more severe course and increased COVID-19–related deaths. Furthermore, experimental studies suggested that key pathophysiological hypertension mechanisms, such as activation of the renin-angiotensin system (RAS), may play a role in COVID-19. In fact, ACE2 (angiotensin-converting-enzyme 2) is the pivotal receptor for SARS-CoV-2 to enter host cells and provides thus a link between COVID-19 and RAS. It was thus anticipated that drugs modulating the RAS including an upregulation of ACE2 may increase the risk for infection with SARS-CoV-2 and poorer outcomes in COVID-19. Since the use of RAS-blockers, ACE inhibitors or angiotensin receptor blockers, represents the backbone of recommended antihypertensive therapy and intense debate about their use in the COVID-19 pandemic has developed. Currently, a direct role of hypertension, independent of age and other comorbidities, as a risk factor for the SARS-COV-2 infection and COVID-19 outcome, particularly death, has not been established. Similarly, both current experimental and clinical studies do not support an unfavorable effect of RAS-blockers or other classes of first line blood pressure lowering drugs in COVID-19. Here, we review available data on the role of hypertension and its management on COVID-19. Conversely, some aspects as to how the COVID-19 affects hypertension management and impacts on future developments are also briefly discussed. COVID-19 has and continues to proof the critical importance of hypertension research to address questions that are important for global health.

scholarly journals Role of Multifunctional Cytoskeletal Filaments in Coronaviridae Infections: Therapeutic Opportunities for COVID-19 in a Nutshell

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1818
Author(s):  
Victor Norris ◽  
Judit Ovádi
Keyword(s):  
Drug Targets ◽  
Controlled Trial ◽  
Host Cells ◽  
Immunomodulatory Agents ◽  
Randomized Controlled ◽  
Treatment And Prevention ◽  
Scientific World ◽  
One Year ◽  
Novel Coronavirus

A novel coronavirus discovered in 2019 is a new strain of the Coronaviridae family (CoVs) that had not been previously identified in humans. It is known as SARS-CoV-2 for Severe Acute Respiratory Syndrome Coronavirus-2, whilst COVID-19 is the name of the disease associated with the virus. SARS-CoV-2 emerged over one year ago and still haunts the human community throughout the world, causing both healthcare and socioeconomic problems. SARS-CoV-2 is spreading with many uncertainties about treatment and prevention: the data available are limited and there are few randomized controlled trial data on the efficacy of antiviral or immunomodulatory agents. SARS-CoV-2 and its mutants are considered as unique within the Coronaviridae family insofar as they spread rapidly and can have severe effects on health. Although the scientific world has been succeeding in developing vaccines and medicines to combat COVID-19, the appearance and the spread of new, more aggressive mutants are posing extra problems for treatment. Nevertheless, our understanding of pandemics is increasing significantly due to this outbreak and is leading to the development of many different pharmacological, immunological and other treatments. This Review focuses on a subset of COVID-19 research, primarily the cytoskeleton-related physiological and pathological processes in which coronaviruses such as SARS-CoV-2 are intimately involved. The discovery of the exact mechanisms of the subversion of host cells by SARS-CoV-2 is critical to the validation of specific drug targets and effective treatments.

scholarly journals Angiotensin-(1-7)—A Potential Remedy for AKI: Insights Derived from the COVID-19 Pandemic

2021 ◽  
Vol 10 (6) ◽  
pp. 1200
Author(s):  
Samuel N. Heyman ◽  
Thomas Walther ◽  
Zaid Abassi
Keyword(s):  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
Ang Ii ◽  
Viral Attachment ◽  
Beneficial Effects ◽  
Membrane Bound ◽  
G Protein Coupled ◽  
Parenchymal Damage

Membrane-bound angiotensin converting enzyme (ACE) 2 serves as a receptor for the Sars-CoV-2 spike protein, permitting viral attachment to target host cells. The COVID-19 pandemic brought into light ACE2, its principal product angiotensin (Ang) 1-7, and the G protein-coupled receptor for the heptapeptide (MasR), which together form a still under-recognized arm of the renin–angiotensin system (RAS). This axis counteracts vasoconstriction, inflammation and fibrosis, generated by the more familiar deleterious arm of RAS, including ACE, Ang II and the ang II type 1 receptor (AT1R). The COVID-19 disease is characterized by the depletion of ACE2 and Ang-(1-7), conceivably playing a central role in the devastating cytokine storm that characterizes this disorder. ACE2 repletion and the administration of Ang-(1-7) constitute the therapeutic options currently tested in the management of severe COVID-19 disease cases. Based on their beneficial effects, both ACE2 and Ang-(1-7) have also been suggested to slow the progression of experimental diabetic and hypertensive chronic kidney disease (CKD). Herein, we report a further step undertaken recently, utilizing this type of intervention in the management of evolving acute kidney injury (AKI), with the expectation of renal vasodilation and the attenuation of oxidative stress, inflammation, renal parenchymal damage and subsequent fibrosis. Most outcomes indicate that triggering the ACE2/Ang-(1-7)/MasR axis may be renoprotective in the setup of AKI. Yet, there is contradicting evidence that under certain conditions it may accelerate renal damage in CKD and AKI. The nature of these conflicting outcomes requires further elucidation.

scholarly journals Coronavirus-Induced Host Cubic Membranes and Lipid-Related Antiviral Therapies: A Focus on Bioactive Plasmalogens

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuru Deng ◽  
Angelina Angelova
Keyword(s):  
Lipid Membrane ◽  
Lung Surfactant ◽  
Severity Of Illness ◽  
Host Cells ◽  
Antiviral Therapies ◽  
Lipid Biomarker ◽  
Lipid Species ◽  
Cardiometabolic Disorders ◽  
Membrane Bound

Coronaviruses have lipid envelopes required for their activity. The fact that coronavirus infection provokes the formation of cubic membranes (CM) (denoted also as convoluted membranes) in host cells has not been rationalized in the development of antiviral therapies yet. In this context, the role of bioactive plasmalogens (vinyl ether glycerophospholipids) is not completely understood. These lipid species display a propensity for non-lamellar phase formation, facilitating membrane fusion, and modulate the activity of membrane-bound proteins such as enzymes and receptors. At the organism level, plasmalogen deficiency is associated with cardiometabolic disorders including obesity and type 2 diabetes in humans. A straight link is perceived with the susceptibility of such patients to SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) infection, the severity of illness, and the related difficulty in treatment. Based on correlations between the coronavirus-induced modifications of lipid metabolism in host cells, plasmalogen deficiency in the lung surfactant of COVID-19 patients, and the alterations of lipid membrane structural organization and composition including the induction of CM, we emphasize the key role of plasmalogens in the coronavirus (SARS-CoV-2, SARS-CoV, or MERS-CoV) entry and replication in host cells. Considering that plasmalogen-enriched lung surfactant formulations may improve the respiratory process in severe infected individuals, plasmalogens can be suggested as an anti-viral prophylactic, a lipid biomarker in SARS-CoV and SARS-CoV-2 infections, and a potential anti-viral therapeutic component of lung surfactant development for COVID-19 patients.

scholarly journals Androgens in SARS-CoV-2 Coronavirus Infections

2021 ◽  
pp. S145-S151
Author(s):  
L STÁRKA ◽  
M DUŠKOVÁ
Keyword(s):  
Androgen Deprivation ◽  
Host Cells ◽  
General Effect ◽  
Androgenic Alopecia ◽  
Cancer Treatments ◽  
Clinical Observations ◽  
Novel Coronavirus ◽  
Prostate Cancer Treatments ◽  
Androgen Levels

Recent molecular biology findings have shown that for the penetration of the SARS-CoV-2 coronavirus into host cells, a key role is played by protease serine 2, the activity of which is dependent on androgens. The important role of androgens is also evidenced by clinical observations that men in some age categories are infected by this novel coronavirus up to two times more frequently than women. In addition, men with androgenic alopecia tend to have more serious clinical courses, while men with androgen deprivation as a result of prostate cancer treatments tend to have milder courses. This is in line with the fact that preadolescent children are only rarely sickened with serious forms of SARS-CoV-2 infections. Even though these observations may be explained by other factors, many authors have hypothesized that lowered androgen levels and blocking their activity using anti-androgen medication may moderate the course of the viral infection in intermediately- to critically-affected cases. Clearly, it would be important for androgen deprivation to block not just gonadal androgens, but also adrenal androgens. On the other hand, low androgen levels are considered to be a risk factor for the course of SARS-CoV-2 infections, either because low androgen levels have a general effect on anabolic-catabolic equilibrium and energy metabolism, or because of the ability of testosterone to modify the immune system. It is not yet clear if infection with this novel coronavirus might induce hypogonadism, leading to undesirable side effects on male fertility.

scholarly journals Correcting the imbalanced protective RAS in COVID-19 with angiotensin AT2-receptor agonists

2020 ◽  
Vol 134 (22) ◽  
pp. 2987-3006 ◽  
Author(s):  
U. Muscha Steckelings ◽  
Colin Sumners
Keyword(s):  
Virus Disease ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
Angiotensin System ◽  
Organ Systems ◽  
Membrane Bound ◽  
Compound 21 ◽  
The Brain ◽  
Entry Mechanism ◽  
Stimulation Of

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for the global corona virus disease 2019 (COVID-19) pandemic enters host cells via a mechanism that includes binding to angiotensin converting enzyme (ACE) 2 (ACE2). Membrane-bound ACE2 is depleted as a result of this entry mechanism. The consequence is that the protective renin–angiotensin system (RAS), of which ACE2 is an essential component, is compromised through lack of production of the protective peptides angiotensin-(1-7) and angiotensin-(1-9), and therefore decreased stimulation of Mas (receptor Mas) and angiotensin AT2-receptors (AT2Rs), while angiotensin AT1-receptors (AT1Rs) are overstimulated due to less degradation of angiotensin II (Ang II) by ACE2. The protective RAS has numerous beneficial actions, including anti-inflammatory, anti-coagulative, anti-fibrotic effects along with endothelial and neural protection; opposite to the deleterious effects caused by heightened stimulation of angiotensin AT1R. Given that patients with severe COVID-19 exhibit an excessive immune response, endothelial dysfunction, increased clotting, thromboses and stroke, enhancing the activity of the protective RAS is likely beneficial. In this article, we discuss the evidence for a dysfunctional protective RAS in COVID and develop a rationale that the protective RAS imbalance in COVID-19 may be corrected by using AT2R agonists. We further review preclinical studies with AT2R agonists which suggest that AT2R stimulation may be therapeutically effective to treat COVID-19-induced disorders of various organ systems such as lung, vasculature, or the brain. Finally, we provide information on the design of a clinical trial in which patients with COVID-19 were treated with the AT2R agonist Compound 21 (C21). This trial has been completed, but results have not yet been reported.

ACE2 as a potential target for management of novel coronavirus (nCoV- 2019)

2020 ◽  
Vol 17 ◽  
Author(s):  
Elham Foroozanfar ◽  
Mohamad Forouzanfar ◽  
Tahereh Farkhondeh ◽  
Saeed Samarghandian ◽  
Fatemeh Forouzanfar
Keyword(s):  
Specific Treatment ◽  
Renin Angiotensin System ◽  
Review Article ◽  
The Other ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
The World ◽  
Novel Coronavirus

Abstract:: A novel coronavirus termed nCoV-2019 caused an epidemic of acute respiratory syndrome in humans was first detected in Wuhan, China, in December 2019. nCoV-2019 resulted in thousands of cases of lethal disease all around the world. Unfortunately, there is no specific treatment yet so better understanding of the pathobiology of the disease can be helpful. The renin–angiotensin system and their products has several important physiological actions, On the other hand, this system involved in the pathogenesis of various diseases. In this context, this review article will briefly insights for understanding the role of angiotensin-converting enzyme 2 (ACE2) receptor as a potential attractive target for nCoV-2019- induced acute respiratory syndrome.

COVID 19: Camostat and The Role of Serine Protease Entry Inhibitor TMPRSS2

2020 ◽  
Author(s):  
Stefan Bittmann
Keyword(s):  
Host Cell ◽  
Serine Protease ◽  
Cellular Protein ◽  
Host Cells ◽  
The Novel ◽  
Robert Koch Institute ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

According to the latest research, the novel coronavirus uses the protein angiotensin-converting enzyme 2 (ACE-2) as a receptor for docking to the host cell. Essential for entry is the priming of the spike (S) protein of the virus by host cell proteases. A broadly based team led by infection biologists from the German Primate Centre and with the participation of the Charité Hospital in Berlin, the Hanover Veterinary University Foundation, the BG-UnfallklinikMurnau, the LMU Munich, the Robert Koch Institute and the German Centre for Infection Research wanted to find out how SARS-CoV-2 enters host cells and how this process can be blocked [1]. They have published their findings in the journal "Cell" [1]. The team of scientists was initially able to confirm that SARS-CoV-2 docks to the host cell via the ACE-2 receptor. They also identified Transmembrane serine protease 2 (TMPRSS2) as the cellular protein responsible for entry into the cell [1-3].

scholarly journals Potential influence of COVID-19/ACE2 on the female reproductive system

2020 ◽  
Vol 26 (6) ◽  
pp. 367-373 ◽  
Author(s):  
Yan Jing ◽  
Li Run-Qian ◽  
Wang Hao-Ran ◽  
Chen Hao-Ran ◽  
Liu Ya-Bin ◽  
...  
Keyword(s):  
Reproductive System ◽  
Sexual Transmission ◽  
Renin Angiotensin System ◽  
Host Cells ◽  
Ang Ii ◽  
Female Reproductive System ◽  
Contact Transmission ◽  
Novel Coronavirus ◽  
And Function ◽  
Mother To Child

Abstract The 2019 novel coronavirus (2019-nCoV) appeared in December 2019 and then spread throughout the world rapidly. The virus invades the target cell by binding to angiotensin-converting enzyme (ACE) 2 and modulates the expression of ACE2 in host cells. ACE2, a pivotal component of the renin-angiotensin system, exerts its physiological functions by modulating the levels of angiotensin II (Ang II) and Ang-(1-7). We reviewed the literature that reported the distribution and function of ACE2 in the female reproductive system, hoping to clarify the potential harm of 2019-nCoV to female fertility. The available evidence suggests that ACE2 is widely expressed in the ovary, uterus, vagina and placenta. Therefore, we believe that apart from droplets and contact transmission, the possibility of mother-to-child and sexual transmission also exists. Ang II, ACE2 and Ang-(1-7) regulate follicle development and ovulation, modulate luteal angiogenesis and degeneration, and also influence the regular changes in endometrial tissue and embryo development. Taking these functions into account, 2019-nCoV may disturb the female reproductive functions through regulating ACE2.

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