scholarly journals Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV

2020 ◽  
Vol 80 (4) ◽  
pp. 469-496 ◽  
Author(s):  
Rui Li ◽  
Songlin Qiao ◽  
Gaiping Zhang
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Receptor Usage ◽  
Novel Coronavirus

scholarly journals ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: the saga continues

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Sally Badawi ◽  
Bassam R. Ali
Keyword(s):  
Cell Surface ◽  
Angiotensin Converting Enzyme ◽  
The Novel ◽  
Converting Enzyme ◽  
Post Translational Modifications ◽  
Angiotensin Converting Enzyme 2 ◽  
Viral Attachment ◽  
Novel Coronavirus ◽  
Effective Medication ◽  
Potential Use

AbstractWith the emergence of the novel coronavirus SARS-CoV-2 since December 2019, more than 65 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases, leading to over 1.5 million deaths globally. Despite the collaborative and concerted research efforts that have been made, no effective medication for COVID-19 (coronavirus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in the human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to tackle the virus through the use of angiotensin-converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2, which does not directly aim to reduce its membrane availability. However, through this review, we present a different perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, and shedding and cellular trafficking pathways including the internalization are not well elucidated in literature. Therefore, we hereby present an overview of the fate of newly synthesized ACE2, its post translational modifications, and what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Moreover, an extensive understanding of these processes is necessarily required to evaluate the potential use of ACE2 as a credible therapeutic target.

scholarly journals Pathological Role of Angiotensin II in Severe COVID-19

TH Open ◽  
2020 ◽  
Vol 04 (02) ◽  
pp. e138-e144 ◽  
Author(s):  
Wolfgang Miesbach
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Treatment Options ◽  
Renin Angiotensin System ◽  
Target Cells ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Novel Coronavirus

AbstractThe activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.

DOCKING STUDY OF NOVEL N-SUBSTITUTED 2,5-BIS[(7-CHLOROQUINOLIN-4-YL)AMINO]PENTANOIC DERIVATIVES AS SELECTIVE HIGH-BINDER WITH ANGIOTENSIN CONVERTING ENZYME 2

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (08) ◽  
pp. 16-24
Author(s):  
Mohammed Oday Ezzat ◽  
Basma M. Abd Razik ◽  
Kutayba F. Dawood
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Active Site ◽  
Docking Study ◽  
World Health ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Pharmaceutical Properties ◽  
Novel Coronavirus

The prevalence of a novel coronavirus (2019-nCoV) in the last few months represents a serious threat as a world health emergency concern. Angiotensin-converting enzyme 2 (ACE2) is the host cellular receptor for the respiratory syndrome of coronavirus epidemic in 2019 (2019-nCoV). In this work, the active site of ACE2 is successfully located by Sitmap prediction tool and validated by different marketed drugs. To design and discover new medical countermeasure drugs, we evaluate a total of 184 molecules of 7-chloro-N-methylquinolin-4-amine derivatives for binding affinity inside the crystal structure of ACE2 located active site. A novel series of N-substituted 2,5-bis[(7-chloroquinolin-4-yl)amino]pentanoic acid derivatives is generated and evaluated for a prospect as a lead compound for (2019-nCoV) medication with a docking score range of (-10.60 to -8.99) kcal/mol for the highest twenty derivatives. Moreover, the ADME pharmaceutical properties were evaluated for further proposed experimental evaluation in vitro or in vivo

scholarly journals Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

2020 ◽  
Vol 94 (7) ◽  
Author(s):  
Yushun Wan ◽  
Jian Shang ◽  
Rachel Graham ◽  
Ralph S. Baric ◽  
Fang Li
Keyword(s):  
Animal Species ◽  
Atomic Level ◽  
Spike Protein ◽  
Structural Studies ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Receptor Usage ◽  
Receptor Recognition ◽  
Critical Residues ◽  
Novel Coronavirus

ABSTRACT Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV’s capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV. IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.

scholarly journals A plausible path to contain the spread of 2019 Novel Coronavirus; a computational analysis prompts to the use of ACE2 receptor blockers

2020 ◽  
Author(s):  
Christopher Whitman
Keyword(s):  
Angiotensin Converting Enzyme ◽  
World Health ◽  
Converting Enzyme ◽  
Time Sharing ◽  
Angiotensin Converting Enzyme 2 ◽  
Bioinformatic Tools ◽  
Receptor Blockers ◽  
Genetic Sequences ◽  
Novel Coronavirus ◽  
Health Organization

Abstract Starting December 30th, 2019, a virus spread from Wuhan, in the Hubei Province of China. The virus had soon been recognized as part of the Coronavirus and temporarily named 2019 Novel Coronavirus. The dramatic increase of infections led to the death of over 400 people, by Feb 4th, 2020. By this day the virus had already crossed into 27 countries. March 11th, 2020 the World Health Organization declared the Novel Coronavirus a pandemic, pointing to over 118,000 cases of infections in over 110 countries. This public health threat drove the international community to real-time sharing of the genetic sequences isolated from the viruses. We used these freely accessible genetic data, while leveraging bioinformatic tools, with the intent to explore possible contributions to address this threat. Angiotensin-converting Enzyme 2 Inhibition has been proven to be a valuable strategy address the spread of SARS. After proving remarkable genetic similarities between SARS and the 2019 Novel Coronavirus, we computationally built the first known ex-novo model of the 2019 Novel Coronavirus Spike Glycoprotein entirely generated from its aminoacidic sequence, using I-TASEER. We then assessed the 2019 Novel Coronavirus interaction with the human Angiotensin-converting Enzyme 2. This research prompts at the potential use of Angiotensin- converting Enzyme 2 receptors blockers, as both clinical and prophylaxis measures to contain the spread of 2019 Novel Coronavirus.

scholarly journals Human genetic basis of coronavirus disease 2019

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hao Deng ◽  
Xue Yan ◽  
Lamei Yuan
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Genetic Basis ◽  
Human Leukocyte ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Leukocyte Antigen ◽  
Host Genetic ◽  
Considerable Morbidity ◽  
Novel Coronavirus ◽  
Hla Genotype

AbstractCoronavirus disease 2019 (COVID-19) caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in considerable morbidity and mortality worldwide. COVID-19 incidence, severity, and mortality rates differ greatly between populations, genders, ABO blood groups, human leukocyte antigen (HLA) genotypes, ethnic groups, and geographic backgrounds. This highly heterogeneous SARS-CoV-2 infection is multifactorial. Host genetic factors such as variants in the angiotensin-converting enzyme gene (ACE), the angiotensin-converting enzyme 2 gene (ACE2), the transmembrane protease serine 2 gene (TMPRSS2), along with HLA genotype, and ABO blood group help to explain individual susceptibility, severity, and outcomes of COVID-19. This review is focused on COVID-19 clinical and viral characteristics, pathogenesis, and genetic findings, with particular attention on genetic diversity and variants. The human genetic basis could provide scientific bases for disease prediction and targeted therapy to address the COVID-19 scourge.

scholarly journals Angiotensin-Converting Enzyme 2 (ACE2) in the Pathogenesis of ARDS in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Keiji Kuba ◽  
Tomokazu Yamaguchi ◽  
Josef M. Penninger
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Neutralizing Antibodies ◽  
Cell Entry ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Angiotensin Converting Enzyme 2 ◽  
Infected People ◽  
Critical Attention ◽  
Novel Coronavirus

Seventeen years after the epidemic of SARS coronavirus, a novel coronavirus SARS-CoV-2-emerged resulting in an unprecedented pandemic. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for cell entry of SARS-CoV-2 as well as the SARS coronavirus. Despite many similarities to SARS coronavirus, SARS-CoV-2 exhibits a higher affinity to ACE2 and shows higher infectivity and transmissibility, resulting in explosive increase of infected people and COVID-19 patients. Emergence of the variants harboring mutations in the receptor-binding domain of the Spike protein has drawn critical attention to the interaction between ACE2 and Spike and the efficacies of vaccines and neutralizing antibodies. ACE2 is a carboxypeptidase which degrades angiotensin II, B1-bradykinin, or apelin, and thereby is a critical regulator of cardiovascular physiology and pathology. In addition, the enzymatic activity of ACE2 is protective against acute respiratory distress syndrome (ARDS) caused by viral and non-viral pneumonias, aspiration, or sepsis. Upon infection, both SARS-CoV-2 and SARS coronaviruses downregulates ACE2 expression, likely associated with the pathogenesis of ARDS. Thus, ACE2 is not only the SARS-CoV-2 receptor but might also play an important role in multiple aspects of COVID-19 pathogenesis and possibly post-COVID-19 syndromes. Soluble forms of recombinant ACE2 are currently utilized as a pan-variant decoy to neutralize SARS-CoV-2 and a supplementation of ACE2 carboxypeptidase activity. Here, we review the role of ACE2 in the pathology of ARDS in COVID-19 and the potential application of recombinant ACE2 protein for treating COVID-19.

scholarly journals Potential Natural Compounds for Preventing SARS-CoV-2 (2019-nCoV) Infection

2020 ◽  
Author(s):  
Hansen Chen ◽  
Qiaohui Du
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Angiotensin Converting Enzyme ◽  
Natural Compounds ◽  
Converting Enzyme ◽  
Active Compounds ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus

SARS-CoV-2 (2019-nCoV), a novel coronavirus, caused the pneumonia outbreak in China and continue to expand. The host receptor for 2019-nCoV Angiotensin-converting enzyme 2 (ACE2), is the same as the host receptor for SARS-CoV. Targeting ACE2 holds the promise for preventing and inhibiting 2019-nCoV infection. Chinese Medicine herbs could be a valuable pool for identifying active compounds for treating infection of 2019-nCoV. In this study, we summarize several active compounds, including baicalin, Scutellarin, Hesperetin, Nicotianamine and glycyrrhizin that could have potential anti-2019-nCoV effects. We conduct molecular docking to predict their capacity for binding ACE2, which may prevent the 2019-nCoV infection. We propose that these selected compounds worth further investigation for preventing 2019-nCoV.

scholarly journals Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3980 ◽  
Author(s):  
Muchtaridi Muchtaridi ◽  
M. Fauzi ◽  
Nur Kusaira Khairul Ikram ◽  
Amirah Mohd Gazzali ◽  
Habibah A. Wahab
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Host Cells ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Converting Enzyme ◽  
Mortality And Morbidity ◽  
Angiotensin Converting Enzyme 2 ◽  
Arterial Blood ◽  
Potential Efficacy ◽  
Novel Coronavirus

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.

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