scholarly journals Molecular Dynamics Reveals Complex Compensatory Effects of Ionic Strength on the Severe Acute Respiratory Syndrome Coronavirus 2 Spike/Human Angiotensin-Converting Enzyme 2 Interaction

2020 ◽  
Vol 11 (24) ◽  
pp. 10446-10453
Author(s):  
Anacleto Silva de Souza ◽  
Jose David Rivera ◽  
Vitor Medeiros Almeida ◽  
Pingju Ge ◽  
Robson Francisco de Souza ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Ionic Strength ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

scholarly journals Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2

2020 ◽  
Author(s):  
Cecylia S. Lupala ◽  
Vikash Kumar ◽  
Xuanxuan Li ◽  
Xiao-dong Su ◽  
Haiguang Liu
Keyword(s):  
Molecular Dynamics ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Computational Analysis ◽  
Spike Protein ◽  
Short Peptides ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Dynamics Simulations

ABSTRACTThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Hence, drugs that can interfere the SARS-CoV-2-RBD binding to hACE2 potentially can inhibit SARS-CoV-2 from entering human cells. Here, based on the N-terminal helix α1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. The important interactions between peptides and RBD are highlighted to provide guidance for the design of peptidomimetics against the SARS-CoV-2.

scholarly journals Do sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression explain increased severity and mortality of COVID-19 in males?

Diagnosis ◽  
2020 ◽  
Vol 7 (4) ◽  
pp. 385-386 ◽  
Author(s):  
Jens Vikse ◽  
Giuseppe Lippi ◽  
Brandon Michael Henry
Keyword(s):  
Mortality Rate ◽  
Severe Acute Respiratory Syndrome ◽  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Immunomodulatory Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Cytopathic Effects ◽  
Severe Lung

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), shares similarities with the former SARS outbreak, which was caused by SARS-CoV-1. SARS was characterized by severe lung injury due to virus-induced cytopathic effects and dysregulated hyperinflammatory state. COVID-19 has a higher mortality rate in men both inside and outside China. In this opinion paper, we describe how sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression may explain the increased severity and mortality of COVID-19 in males. We highlight that immunomodulatory treatment must be tailored to the underlying immunobiology at different stages of disease. Moreover, by investigating sex-based immunobiological differences, we may enhance our understanding of COVID-19 pathophysiology and facilitate improved immunomodulatory strategies.

scholarly journals ACE2 the Janus-faced protein – from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19

2020 ◽  
Vol 134 (7) ◽  
pp. 747-750 ◽  
Author(s):  
Rhian M. Touyz ◽  
Hongliang Li ◽  
Christian Delles
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Basic Science ◽  
Physiological Role ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Multifunctional Protein ◽  
Angiotensin Converting Enzyme 2

Abstract Angiotensin converting enzyme 2 (ACE2) is the major enzyme responsible for conversion of Ang II into Ang-(1-7). It also acts as the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which causes Coronavirus Disease (COVID)-19. In recognition of the importance of ACE2 and to celebrate 20 years since its discovery, the journal will publish a focused issue on the basic science and (patho)physiological role of this multifunctional protein.

scholarly journals The Use of Fabric Masks in Prevention of Community Transmission of COVID-19

2020 ◽  
Vol 8 (2) ◽  
pp. 168-175
Author(s):  
Rudi Saputra
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Respiratory Tract ◽  
Angiotensin Converting Enzyme ◽  
Medical Personnel ◽  
New Disease ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Public Discussion ◽  
The Public ◽  
Community Transmission

Introduction: COVID-19 (Coronavirus Disease 2019) is a new disease due to SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) which can be transmitted through droplets. One effort to prevent transmission of COVID-19 is to use a mask. Medical masks are effective in preventing transmission of COVID-19, but their numbers are very limited and are very much needed by medical personnel when treating COVID-19 patients. Therefore, to prevent the spread of COVID-19 more broadly, alternative medical masks are needed, namely by using cloth masks which have not been discussed much about the purpose of their use to the public. Discussion: SARS-CoV-2 is a cause of COVID-19 and infects the respiratory tract, especially in the lungs (pulmo) through the ACE2 receptor (Angiotensin-Converting Enzyme 2). SARS-CoV-2 has a diameter of around 120 nm. Cloth masks as an alternative to the scarcity of medical masks are recommended for public use. The recommended cloth masks are made of cotton or a cloth towel. A cloth mask is able to hold large droplets (> 5 μm), but not small droplets. Conclusion: Cloth masks can be used by the community in an effort to minimize transmission of COVID-19 by holding large droplets, but it is not effective in preventing transmission of COVID-19 because it can still be passed by SARS-CoV-2. Suggestion: Cloth masks can be optimized using nanoparticles to resist SARS-CoV-2.

scholarly journals Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2

2020 ◽  
Author(s):  
Huihui Mou ◽  
Brian D. Quinlan ◽  
Haiyong Peng ◽  
Yan Guo ◽  
Shoujiao Peng ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Viral Receptor ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Binding Domains ◽  
Protein Receptor ◽  
Horseshoe Bat ◽  
Horseshoe Bats

SUMMARYThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme 2 (ACE2). ACE2 is also the viral receptor of SARS-CoV (SARS-CoV-1), a related coronavirus that emerged in 2002-2003. Horseshoe bats (genus Rhinolophus) are presumed to be the original reservoir of both viruses, and a SARS-like coronavirus, RaTG13, closely related SARS-CoV-2, has been isolated from one horseshoe-bat species. Here we characterize the ability of S-protein receptor-binding domains (RBDs) of SARS-CoV-1, SARS-CoV-2, and RaTG13 to bind a range of ACE2 orthologs. We observed that the SARS-CoV-2 RBD bound human, pangolin, and horseshoe bat (R. macrotis) ACE2 more efficiently than the SARS-CoV-1 or RaTG13 RBD. Only the RaTG13 RBD bound rodent ACE2 orthologs efficiently. Five mutations drawn from ACE2 orthologs of nine Rhinolophus species enhanced human ACE2 binding to the SARS-CoV-2 RBD and neutralization of SARS-CoV-2 by an immunoadhesin form of human ACE2 (ACE2-Fc). Two of these mutations impaired neutralization of SARS-CoV-1. An ACE2-Fc variant bearing all five mutations neutralized SARS-CoV-2 five-fold more efficiently than human ACE2-Fc. These data narrow the potential SARS-CoV-2 reservoir, suggest that SARS-CoV-1 and -2 originate from distinct bat species, and identify a more potently neutralizing form of ACE2-Fc.

scholarly journals METFORMIN USE IN DIABETES PRIOR TO HOSPITALIZATION: EFFECTS ON MORTALITY IN COVID-19

2020 ◽  
Vol 26 (10) ◽  
pp. 1166-1172
Author(s):  
Jinghong Li ◽  
Qi Wei ◽  
Willis X. Li ◽  
Karen C. McCowen ◽  
Wei Xiong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Clinical Data ◽  
Laboratory Data ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

Objective: Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such as metformin, on COVID-19 outcomes remains unclear. Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2. Data from people with T2DM hospitalized for COVID-19 were used to test the hypothesis that metformin use is associated with improved survival in this population. Methods: Retrospective analyses were performed on de-identified clinical data from a major hospital in Wuhan, China, that included patients with T2DM hospitalized for COVID-19 during the recent epidemic. One hundred and thirty-one patients diagnosed with COVID-19 and T2DM were used in this study. The primary outcome was mortality. Demographic, clinical characteristics, laboratory data, diabetes medications, and respiratory therapy data were also included in the analysis. Results: Of these 131 patients, 37 used metformin with or without other antidiabetes medications. Among the 37 metformin-taking patients, 35 (94.6%) survived and 2 (5.4%) did not survive. The mortality rates in the metformin-taking group versus the non-metformin group were 5.4% (2/37) versus 22.3% (21/94). Using multivariate analysis, metformin was found to be an independent predictor of survival in this cohort ( P = .02). Conclusion: This study reveals a significant association between metformin use and survival in people with T2DM diagnosed with COVID-19. These clinical data are consistent with potential benefits of the use of metformin for COVID-19 patients with T2DM. Abbreviations: ACE2 = angiotensin-converting enzyme 2; AMPK = AMP-activated protein kinase; BMI = body mass index; COVID-19 = coronavirus disease 2019; SARSCoV-2 = severe acute respiratory syndrome coronavirus 2; T2DM = type 2 diabetes mellitus

Identification of the interaction between Angiotensin-converting Enzyme Residues and Severe Acute Respiratory Syndrome Coronavirus 2.

2021 ◽  
Vol 27 ◽  
Author(s):  
Youness Kadil ◽  
Mohammed Mouhcine ◽  
Imane Rahmoune ◽  
Houda Filali
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Methodological Study ◽  
Angiotensin Converting Enzyme 2 ◽  
Enveloped Virus ◽  
Positive Sense ◽  
Contact Residues ◽  
Cell Membrane Protein

Introduction: Coronaviruses are an enveloped virus with a positive-sense single-stranded RNA genome. It has been shown that the viral spike S glycoprotein binds to the cell membrane protein angiotensin-converting enzyme 2 as an invasive process of the virus. The aim of this research is the application of a computational approach in the identification of the interaction residues ACE2 with severe acute respiratory syndrome Coronavirus 2. A methodological study to understand the interactions between SARS CoV2 and ACE2, which is essential for the development of a vaccine and an antiviral. Methods: The S protein is cleaved into two subunits, S1 and S2. S1 contains the receptor-binding domain (RBD) which allows the virus to bind directly to the peptidase domain of ACE2. Results: Our results present the overall differences in contact residues between the different chains, and an alignment between the two SARS Viruses, along with a presentation of similarity between them.Then S2 likely plays a role in membrane fusion. Conclusions : The synthesis of our results appears to provide potentially a rational set of objectives that can help in the development of a SARS-CoV-2 vaccine.

scholarly journals Is there an impact of the COVID-19 pandemic on male fertility? The ACE2 connection

2020 ◽  
Vol 318 (6) ◽  
pp. E878-E880 ◽  
Author(s):  
Johnny S. Younis ◽  
Zaid Abassi ◽  
Karl Skorecki
Keyword(s):  
Public Health ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Reproductive System ◽  
Male Fertility ◽  
Time Course ◽  
Public Health Emergency ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Main Host

The viral pandemic of the coronavirus disease 2019 (COVID-19), generated by a novel mutated severe acute respiratory syndrome coronavirus (SARS-CoV-2), has become a serious worldwide public health emergency, evolving exponentially. While the main organ targeted in this disease is the lungs, other vital organs, such as the heart and kidney, may be implicated. The main host receptor of the SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2), a major component of the renin-angiotensin-aldosterone system (RAAS). The ACE2 is also involved in testicular male regulation of steroidogenesis and spermatogenesis. As the SARS-CoV-2 may have the potential to infect the testis via ACE2 and adversely affect male reproductive system, it is essential to commence with targeted studies to learn from the current pandemic, with the possibility of preemptive intervention, depending on the findings and time course of the continuing pandemic.

scholarly journals Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2

2009 ◽  
Vol 83 (11) ◽  
pp. 5451-5465 ◽  
Author(s):  
Naoko Yoshikawa ◽  
Tomoki Yoshikawa ◽  
Terence Hill ◽  
Cheng Huang ◽  
Douglas M. Watts ◽  
...  
Keyword(s):  
T Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Viral Infection ◽  
Inflammatory Responses ◽  
Fatal Outcome ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Inflammatory Infiltrates ◽  
The Brain

ABSTRACT We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8+ T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.

scholarly journals ACE2 receptor expression in testes: implications in coronavirus disease 2019 pathogenesis†

2020 ◽  
Vol 103 (3) ◽  
pp. 449-451 ◽  
Author(s):  
Saguna Verma ◽  
Sarini Saksena ◽  
Hooman Sadri-Ardekani
Keyword(s):  
Reproductive Health ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Receptor Expression ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Male Reproductive Health

Expression of angiotensin-converting enzyme 2, receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is high in the testes, therefore SARS-CoV-2 infection and its association with male reproductive health should be investigated in male coronavirus disease 2019 patients.

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