scholarly journals Angiotensin-converting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin-6 via STAT3 signaling in rheumatoid synovium

Author(s):  
Sho Mokuda ◽  
Tadahiro Tokunaga ◽  
Junya Masumoto ◽  
Eiji Sugiyama

AbstractDetected in December 2019, the coronavirus disease 2019 (COVID-19) has since spread all over the world, resulting in a global pandemic. The disease is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), and its symptoms usually include cough, fever, and gastrointestinal problems. Although the prevalence of rheumatoid arthritis (RA) is about 1 % of the global population and RA patients naturally have a chance of acquiring COVID-19 in this pandemic, no studies have considered the expression of angiotensin-converting enzyme 2 (ACE2) (a receptor for SARS-CoV-2) in synovial tissues. Our presenting data revealed that ACE2 expression was elevated in active rheumatoid synovium, and siRNA against STAT3 was able to downregulate ACE2 expression, which was in turn induced by IL-6 signaling.

2021 ◽  
Vol 12 ◽  
Author(s):  
Elizabeth M. Sajdel-Sulkowska

SARS-CoV-2, primarily considered a respiratory virus, is increasingly recognized as having gastrointestinal aspects based on its presence in the gastrointestinal (GI) tract and feces. SARS-CoV-2 uses as a receptor angiotensin-converting enzyme 2 (ACE-2), a critical member of the renin-angiotensin-aldosterone system (RAAS) involved in the regulation of blood pressure and fluid system. In addition to the systemic endocrine functions, RAAS components are also involved in intracrine and organ-specific local functions. The angiotensin-converting enzyme 2 (ACE-2) is a key component of RAAS and a receptor for SARS-CoV-2. It is expressed in many tissues with gastrointestinal (GI) tract ACE-2 levels far exceeding those in the respiratory tract. SARS-CoV-2 binding to its receptor results in a deficiency of ACE-2 activity in endocrine, intracrine, and local lung and GI tract ACE-2. The local ACE-2 has different organ-specific functions, including hypertension-independent activities; dysregulations of these functions may contribute to multiorgan COVID-19 pathology, its severity, long-term effects, and mortality. We review supporting evidence from this standpoint. Notably, COVID-19 comorbidities involving hypertension, obesity, heart disease, kidney disease, and diabetes are associated with gastrointestinal problems and display ACE-2 deficits. While RAAS inhibitors target both endocrine and intracrine ACE-2 activity, the deficit of the local ACE-2 activity in the lungs and more so in the gut have not been targeted. Consequently, the therapeutic approach to COVID-19 should be carefully reconsidered. Ongoing clinical trials testing oral probiotic bound ACE-2 delivery are promising.


Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1038
Author(s):  
Deborah Giordano ◽  
Luigi De Masi ◽  
Maria Antonia Argenio ◽  
Angelo Facchiano

An outbreak by a new severe acute respiratory syndrome betacoronavirus (SARS-CoV-2) has spread CoronaVirus Disease 2019 (COVID-19) all over the world. Immediately, following studies have confirmed the human Angiotensin-Converting Enzyme 2 (ACE2) as a cellular receptor of viral Spike-Protein (Sp) that mediates the CoV-2 invasion into the pulmonary host cells. Here, we compared the molecular interactions of the viral Sp from previous SARS-CoV-1 of 2002 and SARS-CoV-2 with the host ACE2 protein by in silico analysis of the available experimental structures of Sp-ACE2 complexes. The K417 amino acid residue, located in the region of Sp Receptor-Binding Domain (RBD) of the new coronavirus SARS-CoV-2, showed to have a key role for the binding to the ACE2 N-terminal region. The R426 residue of SARS-CoV-1 Sp-RBD also plays a key role, although by interacting with the central region of the ACE2 sequence. Therefore, our study evidenced peculiarities in the interactions of the two Sp-ACE2 complexes. Our outcomes were consistent with previously reported mutagenesis studies on SARS-CoV-1 and support the idea that a new and different RBD was acquired by SARS-CoV-2. These results have interesting implications and suggest further investigations.


2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Taichiro Minami ◽  
Yasunori Iwata ◽  
Takashi Wada

AbstractThe world today is facing a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which mainly causes a respiratory disease known as coronavirus disease 2019 (COVID-19). Therefore, its pathogenesis and complications should be identified and understood. SARS-CoV-2 infects the host using the angiotensin-converting enzyme 2 (ACE2) as its receptor, which is expressed in several organs including the lungs, heart, kidneys, and intestines. Kidney complications are relatively common, and acute kidney injury (AKI) is a life-threatening complication in patients with COVID-19. In this review, the renal histological patterns of COVID-19 are described in detail, and its potential mechanisms associated with AKI are discussed.


Author(s):  
Amitha Ramesh ◽  
Raksha Potdar ◽  
Rahul Bhandary

AbstractGlobal outbreak of coronavirus disease 2019 (COVID-19) in December 2019 has affected millions of people around the world. This virus binds to angiotensin-converting enzyme-2 receptors present in the pharynx, nose, oral cavity, salivary glands, tongue, etc. Saliva has been shown to have viral loads of COVID-19 as it reported to be 2019-novel-coronavirus nucleic acid positive. This article is based on the association of oral fluids and their role in diagnosis of coronavirus infection.


2021 ◽  
Vol 2 (2) ◽  
pp. 1
Author(s):  
Sukhminder Jit Singh Bajwa ◽  
Ridhima Sharma ◽  
Madhuri S Kurdi

Severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) has affected millions of people across the world engendering an unprecedented pandemic. Coronavirus disease (COVID)-19 can present asymptomatic or in the form of the acute respiratory syndrome, viral pneumonia,or sepsis. Due to the novelty of the disease, the endocrine manifestations are not fully understood. It becomes indispensable to address the underlying endocrine disruptions contributing to the severe form of illness and thereby increasing the mortality.We discuss here the SARS-CoV-2 virus and endocrine reverberations based on the research with structurally similar SARS-COV-1. SARS-CoV-2 enters the body via its attachment to the angiotensin-converting enzyme 2 (ACE2) receptors. Apart from lungs,ACE2 expression on various organs can lead to endocrine perturbations.In COVID-19 infection, pre-existing endocrine disorders warrant cautious management and may require replacement therapy. COVID-19 and its repercussions on hormones are discussed extensively in this review.


Author(s):  
Seyed-Mohammad Ghahestani ◽  
Javad Mahmoudi ◽  
Sakineh Hajebrahimi ◽  
Amir-Babak Sioofy-Khojine ◽  
Hanieh Salehi-Pourmehr ◽  
...  

The new virus SARS-CoV-2 is savagely spreading out over the world. The biologic studies show that the target receptor for the virus might be angiotensin-converting enzyme 2 (ACE2). This peptide is responsible for converting angiotensin II (Ang II), which is a profoundly active peptide, into Ang 1-7 with quite a balancing barbell function. It is emphasized that the direct target of the virus is ACE2 underlining the obvious difference with ACE. Nevertheless, we hypothesized that a back load build up effect on Ang II may usurp the ACE capacity and subsequently leave the bradykinin system unabated. We think there are clinical clues for dry cough and the presumed aggravating role of ACE inhibitors like captopril on the disease process. Thereby, we speculated that inhibition of bradykinin synthesis and/or blockade of bradykinin B2 receptor using Aprotinin/ecallantide and Icatibant, respectively, may hold therapeutic promise in severe cases and these molecules can be advanced to clinical trials.


2020 ◽  
Vol 9 (2) ◽  
pp. e19-e19 ◽  
Author(s):  
Ramin Tolouian ◽  
Sepideh Zununi Vahed ◽  
Shahram Ghiyasvand ◽  
Audrey Tolouian ◽  
Mohammadreza Ardalan

The novel coronavirus disease 2019 (COVID-19) is a rapidly expanding infection around the world. The world Health Organization (WHO) in March 2020 announced the Coronavirus pandemic. This infection causes many deaths on daily basis. Therapeutic options are currently limited. It is revealed that COVID-19 binds to human angiotensin-converting enzyme 2 (ACE2) to enter the host cells. One of the activities of ACE2 is hydrolyzing the active bradykinin metabolite [des-Arg973] BK (DABK). A decreased activity or reducing expression of ACE2 by the virus impairs the inactivation of DABK. This enhances its signaling through the bradykinin B1 receptor (BKB1R) and could lead to fluid extravasation and leukocyte recruitment to the lung. Targeting the bradykinin system by either blocking the bradykinin production or blocking bradykinin receptors may open a new potential therapeutic window for the treatment of COVID-19 induced acute respiratory distress syndrome (ARDS) particularly before patients enter the irreversible stages.


Circulation ◽  
2020 ◽  
Vol 141 (20) ◽  
pp. 1648-1655 ◽  
Author(s):  
Kevin J. Clerkin ◽  
Justin A. Fried ◽  
Jayant Raikhelkar ◽  
Gabriel Sayer ◽  
Jan M. Griffin ◽  
...  

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.


Author(s):  
Xiangyu Chen ◽  
Ren Li ◽  
Zhiwei Pan ◽  
Chunfang Qian ◽  
Yang Yang ◽  
...  

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). To date, no prophylactic vaccines or approved therapeutic agents are available for preventing and treating this highly transmittable disease. Here we report two monoclonal antibodies (mAbs) cloned from memory B cells of patients recently recovered from COVID-19, and both mAbs specifically bind to the spike (S) protein of SARS-CoV-2, block the binding of receptor binding domain (RBD) of SARS-CoV-2 to human angiotensin converting enzyme 2 (hACE2), and effectively neutralize S protein-pseudotyped virus infection. These human mAbs hold the promise for the prevention and treatment of the ongoing pandemic of COVID-19.


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