Molecular insights into the binding variance of SARS-CoV-2 spike with human, cat and dog ACE2 proteins

Author(s):  
Yongjian Zang ◽  
Xuhua Li ◽  
Yizhen Zhao ◽  
He Wang ◽  
Dongxiao Hao ◽  
...  

SARS-CoV-2 has recently caused an epidemic in humans and posed a huge threat to global public health. As a primary receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) exists in different...

2020 ◽  
Vol 318 (6) ◽  
pp. E878-E880 ◽  
Author(s):  
Johnny S. Younis ◽  
Zaid Abassi ◽  
Karl Skorecki

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tarlan Mamedov ◽  
Irem Gurbuzaslan ◽  
Damla Yuksel ◽  
Merve Ilgin ◽  
Gunay Mammadova ◽  
...  

The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread to more than 222 countries and has put global public health at high risk. The world urgently needs a safe, cost-effective SARS-CoV-2 vaccine as well as therapeutic and antiviral drugs to combat COVID-19. Angiotensin-converting enzyme 2 (ACE2), as a key receptor for SARS-CoV-2 infections, has been proposed as a potential therapeutic tool in patients with COVID-19. In this study, we report a high-level production (about ∼0.75 g/kg leaf biomass) of human soluble (truncated) ACE2 in the Nicotiana benthamiana plant. After the Ni-NTA single-step, the purification yields of recombinant plant produced ACE2 protein in glycosylated and deglycosylated forms calculated as ∼0.4 and 0.5 g/kg leaf biomass, respectively. The plant produced recombinant human soluble ACE2s successfully bind to the SARS-CoV-2 spike protein. Importantly, both deglycosylated and glycosylated forms of ACE2 are stable at increased temperatures for extended periods of time and demonstrated strong anti-SARS-CoV-2 activities in vitro. The half maximal inhibitory concentration (IC50) values of glycosylated ACE2 (gACE2) and deglycosylated ACE2 (dACE2) were ∼1.0 and 8.48 μg/ml, respectively, for the pre-entry infection, when incubated with 100TCID50 of SARS-CoV-2. Therefore, plant produced soluble ACE2s are promising cost-effective and safe candidates as a potential therapeutic tool in the treatment of patients with COVID-19.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
PJ Klasse ◽  
John P Moore

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID-19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients, monoclonal antibodies against the viral S-protein, and soluble forms of the receptor for the virus, angiotensin converting enzyme 2. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.


Author(s):  
Otmane El Brini

The coronavirus disease 19 (COVID-19) is a viral infection caused by a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is considered as a public health emergency of international concern. The only available way, apparently effective, to control this pandemic is the social distancing. However, other possible aspects of infection control may be mentioned. In this review, we highlight certain peculiarities linked to the nature of the virus and its angiotensin converting enzyme 2 receptor, the host defense and the final clinical manifestation of the infection that could be essential elements in strengthening the effectiveness of COVID-19 pandemic control efforts.


2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>


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