Expression Levels Of Angiotensin-converting Enzyme 2 Research Articles

Severe Acute Respiratory Syndrome-coronavirus 2 Infection: Role of Angiotensin-converting Enzyme 2

A role of angiotensin-converting enzyme 2 (ACE2) in the coronavirus disease 2019 pandemic has been suggested, because it is the molecular receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2). ACE2 is known to provide a protective effect for cardiac and vascular tissues, because it generally counteracts angiotensin II (Ang II) activity. ACE2 downregulation has been implicated in the pathogenesis of cardiovascular disease. ACE inhibitors and angiotensin receptor blockers may enhance ACE2 mRNA expression and enzyme activity. However, this has not been demonstrated in lung tissue. In the lungs, Ang II induces vasoconstriction to prevent ventilation perfusion mismatch, while also increasing vascular permeability (which can precipitate pulmonary edema). ACE2 is expressed in 0.67% of human lung cells, 80% of which are type 2 alveolar cells. Men (of all ethnicities) and Asian individuals have been shown to express higher levels of ACE2 than women and non-Asian individuals, respectively. However, there are no data from human studies indicating that high ACE2 expression increases the likelihood of SARS-CoV2 infection. In animal studies, an increase in Ang II caused by SARS-CoV2 or spike protein interactions, in turn due to ACE2 downregulation, has been identified as the key mechanism underlying lung injury. In human studies of SARS-CoV2 infection, ACE2 overexpression was shown to cause inflammatory apoptosis and a cytokine storm. The actions of ACE2 and Ang II in SARS-CoV2-infected vascular and lung tissues differ between animals and humans. ACE2 expression levels pre- and post-SARS-CoV2 infection should be differentiated.

Targeting TMPRSS2 in SARS-CoV-2 Infection

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has rapidly caused a global pandemic associated with a novel respiratory infection: coronavirus disease-19 (COVID-19). Angiotensin-converting enzyme-2 (ACE2) is necessary to facilitate SARS-CoV-2 infection, but—owing to its essential metabolic roles—it may be difficult to target it in therapies. Transmembrane protease serine 2 (TMPRSS2), which interacts with ACE2, may be a better candidate for targeted therapies. Using publicly available expression data, we show that both ACE2 and TMPRSS2 are expressed in many host tissues, including lung. The highest expression of ACE2 is found in the testes, whereas the prostate displays the highest expression of TMPRSS2. Given the increased severity of disease among older men with SARS-CoV-2 infection, we address the potential roles of ACE2 and TMPRSS2 in their contribution to the sex differences in severity of disease. We show that expression levels of ACE2 and TMPRSS2 are overall comparable between men and women in multiple tissues, suggesting that differences in the expression levels of TMPRSS2 and ACE2 in the lung and other non–sex-specific tissues may not explain the gender disparities in severity of SARS CoV-2. However, given their instrumental roles for SARS-CoV-2 infection and their pleiotropic expression, targeting the activity and expression levels of TMPRSS2 is a rational approach to treat COVID-19.

Evaluation of COVID-19 based on ACE2 expression in normal and cancer patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is now a serious public health problem. Angiotensin-converting enzyme 2 (ACE2) recognized as the receptor of SARS-CoV is also necessary for SARS-CoV-2. However, the impact of ACE2 on SARS-CoV-2 susceptibility and the situation of malignant tumor patients in this outbreak are unclear. So, it is important to understand the expressions of ACE2 in different normal tissues and cancers. The results showed that the kidneys, duodenum, intestine, gallbladder and testis had the highest ACE2 expressions, followed by the colon, rectum and seminal vesicles. The lungs had a very low expression. ACE2 expressions were upregulated in renal cancer, gastrointestinal tumor and lung cancer. ACE2 expression levels may affect SARS-CoV-2 infection and severity. A total of 3,421 cases with COVID-19 have been collected. Among them, 43 cases (1.26%) had malignant tumor coexisting conditions. The rate of severe events for malignant tumor patients was 39.02% (16/41), while the rate of severe events for all patients was 10.79% (194/1,798). The clinical symptoms and signs were studied for the following three systems: respiratory (31–92%), digestive (10–13%) and urinary systems (3.38%). It seems that symptom severity is not related to protein expression levels. This might be the reason for SARS-CoV-2 showing higher regeneration index and susceptibility. More research is needed to explore the mechanisms and treatments.

The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection.

The serious coronavirus disease‐2019 (COVID‐19) was first reported in December 2019 in Wuhan, China. COVID‐19 is an infectious disease caused by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Angiotensin converting enzyme 2(ACE2) is the cellular receptor for SARS‐CoV‐2. Considering the critical roles of testicular cells for the transmission of genetic information between generations, we analyzed single‐cell RNA‐sequencing (scRNA‐seq) data of adult human testis. The mRNA expression of ACE2 was expressed in both germ cells and somatic cells. Moreover, the positive rate of ACE2 in testes of infertile men was higher than normal, which indicates that SARS‐CoV‐2 may cause reproductive disorders through pathway activated by ACE2 and the men with reproductive disorder may easily to be infected by SARS‐CoV‐2. The expression level of ACE2 was related to the age, and the mid‐aged with higher positive rate than young men testicular cells. Taken together, this research provides a biological background of the potential route for infection of SARS‐CoV‐2 and may enable rapid deciphering male‐related reproductive disorders induced by COVID‐19.

Structural variations and expression profiles of the SARS-CoV-2 host invasion genes in lung cancer.

Recent days have seen growing evidence of cancer's susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and of the effect of genomic differences on the virus' entrance genes in lung cancer. Genetic confirmation of the hypotheses regarding gene expression and mutation pattern of target genes, including angiotensin‐converting enzyme‐2 (ACE2), transmembrane serine protease 2 (TMPRSS2), basigin (CD147/BSG) and paired basic amino acid cleaving enzyme (FURIN/PCSK3), as well as correlation analysis, was done in relation to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) using in silico analysis. Not only were gene expression and mutation patterns detected, but also there were correlation and survival analysis between ACE2 and other target genes expression levels. The total genetic anomaly carrying rate of target genes, including ACE2, TMPRSS2, CD147/BSG, and FURIN/PCSK3, was determined as 8.1% and 21 mutations were detected, with 7 of these mutations having pathogenic features. p.H34N on the RBD binding residues for SARS‐CoV‐2 was determined in our LUAD patient group. According to gene expression analysis results, though the TMPRSS2 level was statistically significantly decreased in the LUSC patient group compared to healthy control, the ACE2 level was determined to be high in LUAD and LUSC groups. There were no meaningful differences in the expression of CD147 and FURIN genes. The challenge for today is building the assessment of genomic susceptibility to COVID‐19 in lung cancer, requiring detailed experimental laboratory studies, in addition to in silico analyses, as a way of assessing the mechanism of novel virus invasion that can be used in the development of effective SARS‐CoV‐2 therapy.

How is the digestive system affected by coronavirus disease?

How is the digestive system affected by coronavirus disease?

A special on epidemic prevention and control: analysis on expression of 2019-nCoV related ACE2 and TMPRSS2 in eye tissues

This article was published ahead of print on the official website of Chinese Journal of Ophthalmolog on Apirl 22,2020. Objective: Angiotensin converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) are the key proteins for 2019-nCoV entry into host cells. To evaluate the potential infection risk of 2019-nCoV on ocular surface, we compared ACE2 and TMPRSS2 expression among different eye tissues. Methods: Experimental study. Thirty mice were assigned to male, female, aged, diabetic and non-diabetic groups, with 6 mice in each group. Real-time PCR was performed to quantify ACE2 and TMPRSS2 gene expression in conjunctiva, cornea, lacrimal gland, iris, lens, retina, lung, heart, kidney, and liver from male mice. Immunohistochemistry staining was applied to visualize the distribution of the two proteins in different mice tissues, and in human corneal and conjunctival sections. Published transcriptome datasets were extracted to generate the expression comparasion of ACE2 and TMPRSS2 between human conjunctival and corneal tissues, and results were analyzed using Mann-Whitney U test. Female mice, aged mice, STZ-induced diabetic mice, diabetic group control mice were also subjected to ACE2 expression analysis. Results were analyzed using Student's t-test. Results: The expression of ACE2 and TMPRSS2 genes were the highest in conjunctiva among all the six mice eye tissues explored. The expression of these two genes in conjunctiva were lower than that in kidney and lung. ACE2 and TMPRSS2 shared similar expression pattern with the staining concentrated in corneal epithelium, conjunctival epithelium and lacrimal gland serous cells. The expression levels of ACE2 showed gender difference. Female mice had lower ACE2 in conjunctiva and cornea than male mice, with the expression levels being only 43% (t=3.269, P=0.031) and 63% (t=4.080, P=0.015) of that in the male conjunctiva and cornea, respectively. Diabetic mice expressed more ACE2 in conjunctiva (1.21-fold, P>0.05) and lacrimal gland (1.10-fold, P>0.05) compared with the control group. No significant difference on ACE2 expression was found between the aged and young adult mice. The expression level of human conjunctiva ACE2 and TMPRSS2 were significantly higher than that in the cornea (P=0.007), with 5.74-fold and 12.84-fold higher in the conjunctiva than in the corneal epithelium cells, which resembled the situation in mice. Conclusion: The observation of high-level ACE2 and TMPRSS2 expression in conjunctiva among the 6 eye tissues examined suggests that conjunctiva serves as an infection target tissue of 2019-nCoV. (Chin J Ophthalmol, 2020, 56:438-446).

Systematic analysis of ACE2 and TMPRSS2 expression in salivary glands reveals underlying transmission mechanism caused by SARS-CoV-2.

Coronavirus disease 2019 (COVID‐19) is a global pandemic that has caused severe health threats and fatalities in almost all communities. Studies have detected severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in saliva with a viral load that lasts for a long period. However, researchers are yet to establish whether SARS‐CoV‐2 can directly enter the salivary glands. Therefore, this study aimed to assess the presence of angiotensin‐converting enzyme 2 (ACE2)/transmembrane serine proteases 2 (TMPRSS2) expression in salivary glands using publicly available databases. The distribution of ACE2 and TMPRSSs family in salivary gland tissue and other tissues was analyzed. The Genotype‐Tissue Expression dataset was employed to explore the ACE2 and TMPRSS2 expression in various body organs and salivary glands in a healthy population. The single‐cell sequencing data for salivary gland samples (including submandibular salivary gland and parotid gland) from mice were collected and analyzed. The components and proportions of salivary gland cells expressing the key protease TMPRSSs family were analyzed. Transcriptome data analysis showed that ACE2 and TMPRSS2 were expressed in salivary glands. The expression levels of ACE2 and TMPRSS2 were marginal without significant differences in different age groups or between men and women. Single‐cell RNA sequence analysis indicated that TMPRSS2 was mainly expressed in salivary gland epithelial cells. We speculate that SARS‐CoV‐2 may be entered in salivary glands.

Utilization of deceased donors during a pandemic: argument against using SARS-CoV-2-positive donors.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rapidly become an unprecedented pandemic that has impacted society, disrupted hospital functions, strained health care resources, and impacted the lives of transplant professionals. Despite this, organ failure and the need for transplant continues throughout the United States. Considering the perpetual scarcity of deceased donor organs, Kates et al present a viewpoint that advocates for the utilization of coronavirus disease 2019 (COVID‐19)–positive donors in selected cases. We present a review of the current literature that details the potential negative consequences of COVID‐19–positive donors. The factors we consider include (1) the risk of blood transmission of SARS‐CoV‐2, (2) involvement of donor organs, (3) lack of effective therapies, (4) exposure of health care and recovery teams, (5) disease transmission and propagation, and (6) hospital resource utilization. While we acknowledge that transplant fulfills the mission of saving lives, it is imperative to consider the consequences not only to our recipients but also to the community and to health care workers, particularly in the absence of effective preventative or curative therapies. For these reasons, we believe the evidence and risks show that COVID‐19 infection should continue to remain a contraindication for donation, as has been the initial response of donation and transplant societies.

Airways Expression of SARS-CoV-2 Receptor, ACE2, and TMPRSS2 Is Lower in Children Than Adults and Increases with Smoking and COPD

It has been reported that angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the main cell entry proteins for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and play a critical role in causing coronavirus disease 2019 (COVID-19). To investigate the expression level of these SARS-CoV-2 host cell entry genes in the lung airway, we used public gene expression datasets. We have found a differential expression of ACE2 and TMPRSS2 in nasal and bronchial airways relative to age and diseases status. Children were found to have significantly lower expression of COVID-19 receptors in the upper and lower airways (nasal and bronchial). Moreover, the lung airway expression of both ACE2 and TMPRSS2 was found to be significantly upregulated in smokers compared with non-smokers, and in patients with chronic obstructive pulmonary disease (COPD) compared with healthy subjects. No difference was observed in the blood expression levels of ACE2 and TMPRSS2 between children and adults, or in COPD or diabetic patients. However, a significant increase in blood expression levels of these genes was observed in patients with essential hypertension, whereas only ACE2 was upregulated in the blood of asthmatics. These results suggest that the observed difference in COVID-19 severity between children and adults could, in part, be attributed to the difference in ACE2 and TMPRSS2 airways tissue expression levels.

Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes.

Being infected by SARS-CoV-2 may cause damage to multiple organs in patients, such as the lung, liver and heart. Angiotensin-converting enzyme 2 (ACE2), reported as a SARS-CoV-2 receptor, is also expressed in human male testes. This suggests a potential risk in human male reproductive system. However, the characteristics of ACE2-positive cells and the expression of other SARS-CoV-2 process-related genes are still worthy of further investigation. Here, we performed singlecell RNA seq (scRNA-seq) analysis on 853 male embryo primordial germ cells (PGCs) and 2,854 normal testis cells to assess the effects of the SARS-CoV-2 virus on the male reproductive system from embryonic stage to adulthood. We also collected and constructed the scRNA-seq library on 228 Sertoli cells from three non-obstructive azoospermia (NOA) patients to assess the effects at disease state. We found that ACE2 expressing cells existed in almost all testis cell types and Sertoli cells had highest expression level and positive cells ratio. Moreover, ACE2 was also expressed in human male PGCs. In adulthood, the level of ACE2 expression decreased with the increase of age. We also found that ACE2 positive cells had high expressions of stress response and immune activation-related genes. Interestingly, some potential SARS-CoV-2 process-related genes such as TMPRSS2, BSG, CTSL and CTSB had different expression patterns in the same cell type. Furthermore, ACE2 expression level in NOA donors’ Sertoli cells was significantly decreased. Our work would help to assess the risk of SARS-CoV-2 infection in the male reproductive system.Electronic Supplementary MaterialSupplementary material is available for this article at 10.1007/s11427-020-1705-0 and is accessible for authorized users.

SARS-CoV-2 receptor ACE2-dependent implications on the cardiovascular system: From basic science to clinical implications

The current COVID-19 pandemic started several months ago and is still exponentially growing in most parts of the world – this is the most recent and alarming update. COVID-19 requires the collaboration of nearly 200 countries to curb the spread of SARS-CoV-2 while gaining time to explore and improve treatment options especially for cardiovascular disease (CVD) and immunocompromised patients, who appear to be at high-risk to die from cardiopulmonary failure. Currently unanswered questions are why elderly people, particularly those with pre-existing comorbidities seem to exhibit higher mortality rates after SARS-CoV-2 infection and whether intensive care becomes indispensable for these patients to prevent multi-organ failure and sudden death. To face these challenges, we here summarize the molecular insights into viral infection mechanisms and implications for cardiovascular disease. Since the infection starts in the upper respiratory system, first flu-like symptoms develop that spread throughout the body. The wide range of affected organs is presumably based on the common expression of the major SARS-CoV-2 entry-receptor angiotensin-converting enzyme 2 (ACE2). Physiologically, ACE2 degrades angiotensin II, the master regulator of the renin-angiotensin-aldosterone system (RAAS), thereby converting it into vasodilatory molecules, which have well-documented cardio-protective effects. Thus, RAAS inhibitors, which may increase the expression levels of ACE2, are commonly used for the treatment of hypertension and CVD. This, and the fact that SARS-CoV-2 hijacks ACE2 for cell-entry, have spurred controversial discussions on the role of ACE2 in COVID-19 patients. In this review, we highlight the state-of-the-art knowledge on SARS-CoV-2-dependent mechanisms and the potential interaction with ACE2 expression and cell surface localization. We aim to provide a list of potential treatment options and a better understanding of why CVD is a high risk factor for COVID-19 susceptibility and further discuss the acute as well as long-term cardiac consequences.

Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues

BackgroundSince its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.MethodsWe compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student’s t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson’s correlation test.ResultsACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.ConclusionsOur data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.

ACE2 correlated with immune infiltration serves as a prognostic biomarker in endometrial carcinoma and renal papillary cell carcinoma: implication for COVID-19.

Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What’s more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.

Genetic Roadmap for Kidney Involvement of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.

The outbreak of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic with an exponential growth rate. A recent study found SARS-CoV-2 nucleocapsid protein in kidney tubules of patients infected with SARS-CoV-2 (B. Diao, C.H. Wang, R.S. Wang, Z.Q. Feng

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Modulation of Angiotensin Converting Enzyme 2 Activity by Ubiquitination

The major roles on the regulation of cardio‐vascular activity of angiotensin II (angII), the main effector hormone of the renin angiotensin system (RAS), were firmly established. These effects are mediated in large part by activation of angiotensin type 1 receptor (AT1R). Angiotensin converting enzyme 2 (ACE2) catalyzes the conversion of angII to angiotensin1‐7 (ang1‐7), which exerts opposite effects to AT1R activation, presumably through MAS1 receptor. Our group previously demonstrated that angII enhanced AT1R/ACE2 interactions which leads to enzyme ubiquitination followed by its degradation into lysosomes. The levels of protein ubiquitination are controlled by an enzymatic cascade involving ubiquitin activating enzymes (E1), ubiquitin conjugating enzymes (E2) and ubiquitin ligases (E3). Ubiquitination can be reversed under the actions of deubiquitinating enzymes (DUBs). In this study, we aimed to characterize the mechanisms modulating ACE2 ubiquitination. Treatment with angII (100 nM for 4h) of ACE2‐transfected HEK293T cells induced a significant decrease in the enzymatic activity (72.21±12.9 % from control n=8), which was reflected in a decrease of its expression levels by 64.45±7.3 (n=3) after 18h. Pretreatment with the effective concentration of PYR‐41, a cell permeable inhibitor of E1 (50 μM for 2h), fully reversed the effects of angII (100.67±23.2% from control, n=9). In contrast, pretreatment with PR‐619, a broad‐spectrum reversible inhibitor of cysteine‐reactive DUBs (20μM, 6h), did not change the effects of angII on ACE2 activity and expression levels (60.93±9.21% from control, n=9). Furthermore, our preliminary proteomic experiments indicated that the expression levels of several E3 ligases were significantly augmented in hypothalami from DOCA‐salt hypertensive mice, including NEDD4 (Neural precursor cell‐Expressed Developmentally Downregulated gene 4). Accordingly, overexpression of NEDD4 in ACE2‐transfected HEK293T cells significantly reduced basal ACE2 activity to 56±7.5 % from control (n=12) and its expression levels (48.97±2.45 %, n=2). Remarkably, angII effects on ACE2 activity and expression levels were eliminated in cells transfected with a catalytically inactive NEDD4 dominant negative mutant (125 ± 5.25%, n=12, and 94.51±15.56, n=2, respectively from control), indicating that angII requires NEDD4 activity to attenuate ACE2 actions. Similarly, angII treatment was unable to change the activity of an ACE2 ubiquitination‐deficient mutant. This mutant also displayed enhanced ACE2 activity in basal conditions (195±4.5%, n=12). In summary, NEDD4 modulates the levels of ACE2 ubiquitination, whereas PYR‐41 prevented the effects of angII on ACE2, indicating that ubiquitination may represent a novel target for the treatment of cardio‐vascular diseases.Support or Funding InformationThis work was supported in part by a Bridge Grant from Howard University to CMF, National Institute of General Medical Sciences P30 GM106392 to JJG and Veterans Affairs Merit Award (BX004294) and LSUHSC‐NO Research Enhancement Program to EL.

Coronavirus Disease 2019 (COVID-19): Do Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Have a Biphasic Effect?

Coronavirus Disease 2019 (COVID-19): Do Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Have a Biphasic Effect?

Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms.

The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host–virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement.

Possible protective role of 17β-estradiol against COVID-19.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19); a worldwide pandemic as declared by the World Health Organization (WHO). SARS-CoV-2 appears to infect cells by first binding and priming its viral-spike proteins with membrane-associated angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Through the coordinated actions of ACE2 and TMPRSS2, SARS-CoV-2 spike proteins fuse with plasma membranes and ultimately the virus enters cells. ACE2 is integral to the renin-angiotensin-aldosterone system (RAAS), and SARS-CoV-2 down-regulates protein expression levels of ACE2. Once infected, patients typically develop acute respiratory distress syndrome (ARDS) and a number of other severe complications that result in a high rate of fatality, especially in older (>60 years) adults and in people with pre-existing medical conditions. Data now indicate clearly that among people of all age groups, COVID-19 fatalities are higher in men than women. Here, attention is focused on these sex differences and posit a role of estrogen in these differences as well as possible therapeutic and protective actions of 17β-estradiol against COVID-19.