Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 59
Filter
Add filters

Year range
1.
Curr Hypertens Rep ; 22(9): 62, 2020 08 27.
Article in English | MEDLINE | ID: covidwho-734061

ABSTRACT

PURPOSE OF REVIEW: Angiotensin-converting enzyme 2 (ACE2), a specific high-affinity angiotensin II-hydrolytic enzyme, is the vector that facilitates cellular entry of SARS-CoV-1 and the novel SARS-CoV-2 coronavirus. SARS-CoV-2, which crossed species barriers to infect humans, is highly contagious and associated with high lethality due to multi-organ failure, mostly in older patients with other co-morbidities. RECENT FINDINGS: Accumulating clinical evidence demonstrates that the intensity of the infection and its complications are more prominent in men. It has been postulated that potential functional modulation of ACE2 by estrogen may explain the sex difference in morbidity and mortality. We review here the evidence regarding the role of estrogenic hormones in ACE2 expression and regulation, with the intent of bringing to the forefront potential mechanisms that may explain sex differences in SARS-CoV-2 infection and COVID-19 outcomes, assist in management of COVID-19, and uncover new therapeutic strategies.


Subject(s)
Coronavirus Infections/etiology , Estrogens/physiology , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/etiology , Sex Factors , Betacoronavirus , Female , Humans , Male , Pandemics
2.
Hypertension ; 76(3): 651-661, 2020 09.
Article in English | MEDLINE | ID: covidwho-714225

ABSTRACT

Discovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B0AT1, in gut. But the current interest in ACE2 arises because it is the cell surface receptor for the novel coronavirus, severe acute respiratory syndrome coronavirus-2, to infect host cells, similar to severe acute respiratory syndrome coronavirus-2. This suggests that ACE2 be considered harmful, however, because of its important other roles, it is paradoxically a potential therapeutic target for cardiopulmonary diseases, including coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2. This review describes the discovery of ACE2, its physiological functions, and its place in the renin-angiotensin system. It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells. Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.


Subject(s)
Coronavirus Infections , Hypertension, Pulmonary , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral , Betacoronavirus/physiology , Coronavirus Infections/metabolism , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Disease Management , Humans , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/virology , Pneumonia, Viral/metabolism , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Renin-Angiotensin System/physiology
6.
Obes Res Clin Pract ; 14(4): 295-300, 2020.
Article in English | MEDLINE | ID: covidwho-643477

ABSTRACT

BACKGROUND: Obesity is a global disease with at least 2.8 million people dying each year as a result of being overweight or obese according to the world health organization figures. This paper aims to explore the links between obesity and mortality in COVID-19. METHODS: Electronic search was made for the papers studying obesity as a risk factor for mortality following COVID-19 infection. Three authors independently selected the papers and agreed for final inclusion. The outcomes were the age, gender, body mass index, severe comorbidities, respiratory support and the critical illness related mortality in COVID-19. 572 publications were identified and 42 studies were selected including one unpublished study data. Only 14 studies were selected for quantitative analysis. RESULTS: All the primary points but the gender are significantly associated with COVID-19 mortality. The age >70, [odd ratio (OR): 0.17, CI; 95%, P-value: <0.00001], gender [OR: 0.89; CI: 95%, P-value: 0.32], BMI > 25 kg/m2 [OR: 3.68, CI: 95%, P-value: <0.003], severe comorbidities [OR: 1.84, CI:95%, P-value: <0.00001], advanced respiratory support [OR: 6.98, CI: 95%, P-value: <0.00001], and critical illness [OR: 2.03, CI: 95%, P-value: <0.00001]. CONCLUSIONS: Patients with obesity are at high risk of mortality from COVID-19 infection.


Subject(s)
Betacoronavirus , Coronavirus Infections/mortality , Obesity/complications , Pneumonia, Viral/mortality , Adult , Aged , Aged, 80 and over , Body Mass Index , Coronavirus Infections/etiology , Female , Humans , Male , Middle Aged , Obesity/immunology , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/etiology
8.
Crit Care ; 24(1): 422, 2020 07 13.
Article in English | MEDLINE | ID: covidwho-641221

ABSTRACT

An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1-7), and the ACE2/angiotensin-(1-7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1-7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1-7)/MAS may help attenuate organ injuries. SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.


Subject(s)
Coronavirus Infections/enzymology , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/enzymology , Humans , Pandemics
9.
Endocrinology ; 161(9)2020 09 01.
Article in English | MEDLINE | ID: covidwho-639100

ABSTRACT

The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.


Subject(s)
Angiotensin II/metabolism , Betacoronavirus/physiology , Diabetes Complications/virology , Endocrine System Diseases/virology , Peptidyl-Dipeptidase A/physiology , Animals , Betacoronavirus/pathogenicity , Brain , Coronavirus Infections/complications , Endocrine System Diseases/complications , Gene Expression , Humans , Hypogonadism/complications , Hypogonadism/virology , Mice , Pandemics , Peptidyl-Dipeptidase A/genetics , Pituitary Diseases/complications , Pituitary Diseases/virology , Pneumonia, Viral/complications , Rats , Renin-Angiotensin System , Serine Endopeptidases/genetics , Thyroid Diseases/complications , Thyroid Diseases/virology
10.
Commun Biol ; 3(1): 374, 2020 07 08.
Article in English | MEDLINE | ID: covidwho-640282

ABSTRACT

The recent outbreak of infections and the pandemic caused by SARS-CoV-2 represent one of the most severe threats to human health in more than a century. Emerging data from the United States and elsewhere suggest that the disease is more severe in men. Knowledge gained, and lessons learned, from studies of the biological interactions and molecular links that may explain the reasons for the greater severity of disease in men, and specifically in the age group at risk for prostate cancer, will lead to better management of COVID-19 in prostate cancer patients. Such information will be indispensable in the current and post-pandemic scenarios.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Prostatic Neoplasms/epidemiology , Sex Distribution , Antineoplastic Agents, Hormonal/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/physiology , Betacoronavirus/ultrastructure , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Disease Susceptibility , Drug Repositioning , Female , Forecasting , Gonadal Steroid Hormones/physiology , Humans , Male , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/physiology , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Protease Inhibitors/therapeutic use , Receptors, Virus/drug effects , Receptors, Virus/physiology , Risk Factors , Serine Endopeptidases/biosynthesis , Serine Endopeptidases/physiology , United States/epidemiology , Virus Internalization
11.
J Nephrol ; 33(4): 737-745, 2020 08.
Article in English | MEDLINE | ID: covidwho-617317

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite its international aggressive extension, with a significant morbidity and mortality, the impact of renal function on its prognosis is uncertain. METHODS: Analysis from the international HOPE-Registry (NCT04334291). The objective was to evaluate the association between kidney failure severity on admission with the mortality of patients with SARS-CoV-2 infection. Patients were categorized in 3 groups according to the estimated glomerular filtration rate on admission (eGFR > 60 mL/min/1.73 m2, eGFR 30-60 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2). RESULTS: 758 patients were included: mean age was 66 ± 18 years, and 58.6% of patient were male. Only 8.5% of patients had a history of chronic kidney disease (CKD); however, 30% of patients had kidney dysfunction upon admission (eGFR < 60 mL/min/1.73 m2). These patients received less frequently pharmacological treatment with hydroxychloroquine or antivirals and had a greater number of complications such as sepsis (11.9% vs 26.4% vs 40.8%, p < 0.001) and respiratory failure (35.4% vs 72.2% vs 62.0%, p < 0.001) as well as a higher in-hospital mortality rate (eGFR > 60 vs eGFR 30-60 vs and eGFR < 30, 18.4% vs 56.5% vs 65.5%, p < 0.001). In multivariate analysis: age, hypertension, renal function, 02 saturation < 92% and lactate dehydrogenase elevation on admission independently predicted all-cause mortality. CONCLUSIONS: Renal failure on admission in patients with SARS-CoV-2 infection is frequent and is associated with a greater number of complications and in-hospital mortality. Our data comes from a multicenter registry and therefore does not allow to have a precise mortality risk assessment. More studies are needed to confirm these findings.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Glomerular Filtration Rate/physiology , Pneumonia, Viral/epidemiology , Registries , Acute Kidney Injury/epidemiology , Aged , Aged, 80 and over , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Risk Assessment
12.
Curr Hypertens Rep ; 22(7): 44, 2020 06 26.
Article in English | MEDLINE | ID: covidwho-615149

ABSTRACT

PURPOSE OF THE REVIEW: Angiotensin-converting enzyme 2 (ACE2) is a key counter-regulatory component of the renin-angiotensin system. Here, we briefly review the mechanistic and target organ effects related to ACE2 activity, and the importance of ACE2 in SARS-CoV-2 infection. RECENT FINDINGS: ACE2 converts angiotensin (Ang) II to Ang-(1-7), which directly opposes the vasoconstrictive, proinflammatory, and prothrombotic effects of Ang II. ACE2 also facilitates SARS-CoV-2 viral entry into host cells. Drugs that interact with the renin-angiotensin system may impact ACE2 expression and COVID-19 pathogenesis; however, the magnitude and direction of these effects are unknown at this time. High quality research is needed to improve our understanding of how agents that act on the renin-angiotensin system impact ACE2 and COVID-19-related disease outcomes.


Subject(s)
Coronavirus Infections/physiopathology , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/physiopathology , Renin-Angiotensin System , Betacoronavirus , Humans , Pandemics , Receptors, Virus/physiology
13.
Am J Physiol Lung Cell Mol Physiol ; 319(2): L277-L288, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-608349

ABSTRACT

In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early imaging studies documented that pulmonary vascular thickening was specifically associated with COVID-19 pneumonia, implying a potential tropism of the virus for the pulmonary vasculature. Moreover, SARS-CoV-2 infection is associated with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, DNA damage, and lung coagulopathy promoting endothelial dysfunction and microthrombosis. These features are strikingly similar to what is seen in pulmonary vascular diseases. Although the consequences of COVID-19 on the pulmonary circulation remain to be explored, several viruses have been previously thought to be involved in the development of pulmonary vascular diseases. Patients with preexisting pulmonary vascular diseases also appear at increased risk of morbidity and mortality. The present article reviews the molecular factors shared by coronavirus infection and pulmonary vasculature defects, and the clinical relevance of pulmonary vascular alterations in the context of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Lung Diseases/etiology , Lung/blood supply , Lung/physiopathology , Pneumonia, Viral/complications , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Cytokines/blood , DNA Damage , Heart Injuries/etiology , Host Microbial Interactions/physiology , Humans , Hypoxia/etiology , Inflammation Mediators/blood , Lung/virology , Lung Diseases/physiopathology , Lung Diseases/virology , Mitochondria/physiology , Myocardium , Oxidative Stress , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Pulmonary Circulation , Pulmonary Embolism/etiology , Receptors, Virus/physiology , Risk Factors , Vasculitis/etiology
14.
Prehosp Disaster Med ; 35(4): 438-441, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-604157

ABSTRACT

Studies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Betacoronavirus , Coronavirus Infections/mortality , Female , Gonadal Steroid Hormones/immunology , Humans , Male , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/mortality , Severity of Illness Index , Sex Factors
15.
Aging (Albany NY) ; 12(12): 11263-11276, 2020 06 16.
Article in English | MEDLINE | ID: covidwho-601536

ABSTRACT

The outbreak of COVID-19 has now become a global pandemic that has severely impacted lives and economic stability. There is, however, no effective antiviral drug that can be used to treat COVID-19 to date. Built on the fact that SARS-CoV-2 initiates its entry into human cells by the receptor binding domain (RBD) of its spike protein binding to the angiotensin-converting enzyme 2 (hACE2), we extended a recently developed approach, EvoDesign, to design multiple peptide sequences that can competitively bind to the SARS-CoV-2 RBD to inhibit the virus from entering human cells. The protocol starts with the construction of a hybrid peptidic scaffold by linking two fragments grafted from the interface of the hACE2 protein (a.a. 22-44 and 351-357) with a linker glycine, which is followed by the redesign and refinement simulations of the peptide sequence to optimize its binding affinity to the interface of the SARS-CoV-2 RBD. The binding experiment analyses showed that the designed peptides exhibited a significantly stronger binding potency to hACE2 than the wild-type hACE2 receptor (with -53.35 vs. -46.46 EvoEF2 energy unit scores for the top designed and wild-type peptides, respectively). This study demonstrates a new avenue to utilize computationally designed peptide motifs to treat the COVID-19 disease by blocking the critical spike-RBD and hACE2 interactions.


Subject(s)
Coronavirus Infections/drug therapy , Peptides/chemical synthesis , Peptides/pharmacology , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/physiology , Amino Acid Sequence , Antiviral Agents , Binding Sites , Drug Design , Evolution, Molecular , Humans , Models, Molecular , Pandemics , Protein Binding , Protein Conformation , Virus Internalization/drug effects
18.
Endocr Relat Cancer ; 27(9): R281-R292, 2020 09.
Article in English | MEDLINE | ID: covidwho-577793

ABSTRACT

The current pandemic (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health challenge with active development of antiviral drugs and vaccines seeking to reduce its significant disease burden. Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist. TMPRSS2 is an androgen-responsive gene and its fusion represents one of the most frequent alterations in prostate cancer. Androgen suppression by androgen deprivation therapy and androgen receptor signaling inhibitors form the foundation of prostate cancer treatment. In this review, we highlight the growing evidence in support of androgen regulation of TMPRSS2 and ACE2 and the potential clinical implications of using androgen suppression to downregulate TMPRSS2 to target SARS-CoV-2. We also discuss the future directions and controversies that need to be addressed in order to establish the viability of targeting TMPRSS2 and/or ACE2 through androgen signaling regulation for COVID-19 treatment, particularly its relevance in the context of prostate cancer management.


Subject(s)
Androgen Antagonists/therapeutic use , Betacoronavirus , Coronavirus Infections/etiology , Pneumonia, Viral/etiology , Prostatic Neoplasms/drug therapy , Androgens/physiology , Coronavirus Infections/drug therapy , Humans , Hypothalamo-Hypophyseal System/physiology , Male , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/drug therapy , Serine Endopeptidases/physiology
20.
Kaohsiung J Med Sci ; 36(6): 389-392, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-505606

ABSTRACT

The spike glycoprotein on the virion surface docking onto the angiotensin-converting enzyme (ACE) 2 dimer is an essential step in the process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in human cells-involves downregulation of ACE2 expression with systemic renin-angiotensin system (RAS) imbalance and promotion of multi-organ damage. In general, the RAS induces vasoconstriction, hypertension, inflammation, fibrosis, and proliferation via the ACE/Ang II/Ang II type 1 receptor (AT1R) axis and induces the opposite effects via the ACE2/Ang (1-7)/Mas axis. The RAS may be activated by chronic inflammation in hypertension, diabetes, obesity, and cancer. SARS-CoV-2 induces the ACE2 internalization and shedding, leading to the inactivation of the ACE2/Ang (1-7)/Mas axis. Therefore, we hypothesize that two hits to the RAS drives COVID-19 progression. In brief, the first hit originates from chronic inflammation activating the ACE/Ang II/AT1R axis, and the second originates from the COVID-19 infection inactivating the ACE2/Ang (1-7)/Mas axis. Moreover, the two hits to the RAS may be the primary reason for increased mortality in patients with COVID-19 who have comorbidities and may serve as a therapeutic target for COVID-19 treatment.


Subject(s)
Betacoronavirus , Coronavirus Infections/physiopathology , Pneumonia, Viral/physiopathology , Renin-Angiotensin System/physiology , Angiotensin II/physiology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Humans , Models, Biological , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Receptor, Angiotensin, Type 1/physiology , Renin-Angiotensin System/drug effects , Spike Glycoprotein, Coronavirus/physiology
SELECTION OF CITATIONS
SEARCH DETAIL