scholarly journals Bioengineered probiotics to control SARS-CoV-2 infection

2020 ◽  
Vol 6 ◽  
Author(s):  
Shantibhusan Senapati ◽  
Jayalaxmi Dash ◽  
Manisha Sethi ◽  
Subhankar Chakraborty
Keyword(s):  
Virus Disease ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Global Public Health ◽  
Health Crisis ◽  
Angiotensin Converting Enzyme 2 ◽  
Public Health Crisis ◽  
Biochemical Studies ◽  
Viral Outbreak ◽  
Novel Therapeutic

The outbreak of 2019 novel corona virus disease (COVID-19) is now a global public health crisis and declared as a pandemic. Several recent studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to human angiotensin-converting enzyme 2 (ACE2). The information obtained from these structural and biochemical studies provides a strong rationale to target SARS-CoV-2 spike protein and ACE2 interaction for developing therapeutics against this viral infection. Here, we propose to discuss the scope of bioengineered probiotics expressing human ACE2 as a novel therapeutic to control the viral outbreak.

scholarly journals “Molecular Masks” for ACE2 to Effectively and Safely Block SARS-CoV-2 Virus Entry

2021 ◽  
Vol 22 (16) ◽  
pp. 8963
Author(s):  
Satya Prakash Shukla ◽  
Kwang Bog Cho ◽  
Vineeta Rustagi ◽  
Xiang Gao ◽  
Xinping Fu ◽  
...  
Keyword(s):  
Virus Entry ◽  
Cell Surface Receptor ◽  
Spike Protein ◽  
Pressure Regulation ◽  
Converting Enzyme ◽  
Normal Blood Pressure ◽  
Health Crisis ◽  
Angiotensin Converting Enzyme 2 ◽  
Surface Receptor ◽  
Unique Cell

Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor angiotensin-converting enzyme 2 (ACE2), which allows the virus to enter the human body. Using our unique cell screening technology, we identified two ACE2-binding peptoid compounds and developed dimeric derivatives (ACE2P1D1 and ACE2P2D1) that effectively blocked spike protein-ACE2 interaction, resulting in the inhibition of SARS-CoV-2 pseudovirus entry into human cells. ACE2P1D1 and ACE2P2D1 also blocked infection by a D614G mutant pseudovirus. More importantly, these compounds do not decrease ACE2 expression nor its enzyme activity (which is important in normal blood pressure regulation), suggesting safe applicability in humans

scholarly journals High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity

2020 ◽  
Vol 295 (52) ◽  
pp. 18579-18588 ◽  
Author(s):  
Jinghua Lu ◽  
Peter D. Sun
Keyword(s):  
Spike Protein ◽  
The Novel ◽  
Global Public Health ◽  
Health Crisis ◽  
Peptide Substrates ◽  
Angiotensin Converting Enzyme 2 ◽  
High Affinity ◽  
Enzymatic Function ◽  
Biological Substrates ◽  
Entry Receptor

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.

scholarly journals Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Furong Liu ◽  
Xin Long ◽  
Wenbin Zou ◽  
Minghao Fang ◽  
Wenjuan Wu ◽  
...  
Keyword(s):  
Clinical Work ◽  
Pancreatic Injury ◽  
Exocrine Glands ◽  
Global Public Health ◽  
Rna Seq ◽  
Health Crisis ◽  
Angiotensin Converting Enzyme 2 ◽  
Public Health Crisis ◽  
Public Datasets ◽  
Possible Cause

AbstractThe ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in the end of 2019 in China has triggered a global public health crisis. Previous studies have shown that SARS-CoV-2 infects cells by binding angiotensin-converting enzyme 2 (ACE2), which is the same as SARS-CoV. The expression and distribution of ACE2 in the pancreas are unknown. At the same time, the injury of pancreas after SARS-CoV-2 infection has not been concerned. Here, we collected public datasets (bulk RNA-seq and single-cell RNA-seq) to indicate the expression and the distribution of ACE2 in pancreas (in both exocrine glands and islets). And further, clinical data including mild and severe patients with COVID-19 demonstrated there existed mild pancreatitis. In the 67 severe cases, 11 patients (16.41%) showed elevated levels of both amylase and lipase, and 5 patients (7.46%) showed imaging alterations. Only one patient (1.85%) showed elevated levels of both amylase and lipase in 54 mild cases, without imaging changes. Our study revealed the phenomenon and possible cause of mild pancreatic injury in patients with COVID-19. This suggests that pancreatitis after SARS-CoV-2 infection should also be paid attention in clinical work.

scholarly journals A collection of designed peptides to target SARS-Cov-2 – ACE2 interaction: PepI-Covid19 database

2020 ◽  
Author(s):  
Ruben Molina ◽  
Baldo Oliva ◽  
Narcis Fernandez-Fuentes
Keyword(s):  
Scientific Community ◽  
Therapeutic Agents ◽  
Spike Protein ◽  
Structural Basis ◽  
Cellular Receptor ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Potential Impact ◽  
Novel Therapeutic

AbstractThe angiotensin-converting enzyme 2 is the cellular receptor used by SARS coronavirus SARS-CoV and SARS-CoV-2 to enter the cell. Both coronavirus use the receptor-binding domain (RBD) of their viral spike protein to interact with ACE2. The structural basis of these interactions are already known, forming a dimer of ACE2 with a trimer of the spike protein, opening the door to target them to prevent the infection. Here we present PepI-Cov19 database, a repository of peptides designed to target the interaction between the RDB of SARS-CoV-2 and ACE2 as well as the dimerization of ACE2 monomers. The peptides were modelled using our method PiPreD that uses native elements of the interaction between the targeted protein and cognate partner that are subsequently included in the designed peptides. These peptides recapitulate stretches of residues present in the native interface plus novel and highly diverse conformations that preserve the key interactions on the interface. PepI-Covid19 database provides an easy and convenient access to this wealth of information to the scientific community with the view of maximizing its potential impact in the development of novel therapeutic agents.

scholarly journals Analysis of SARS-CoV-2 Spike Protein as The Key Target in the Development of Antiviral Candidates for COVID-19 through Computational Study

2021 ◽  
Vol 5 (4) ◽  
pp. 347-352
Author(s):  
Taufik Muhammad Fakih ◽  
Mentari Luthfika Dewi
Keyword(s):  
Binding Sites ◽  
Computational Study ◽  
Docking Simulation ◽  
Competitive Inhibitor ◽  
Protein Docking ◽  
Spike Protein ◽  
Health Crisis ◽  
Angiotensin Converting Enzyme 2 ◽  
Public Health Crisis ◽  
Spike Proteins

The recent public health crisis is threatening the world with the emergence of the spread of the new coronavirus 2019 (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus originates from bats and is transmitted to humans through unknown intermediate animals in Wuhan, China in December 2019. Advances in technology have opened opportunities to find candidates for natural compounds capable of preventing and controlling COVID-19 infection through inhibition of spike proteins of SARS-CoV-2. This research aims to identify, evaluate, and explore the structure of spike protein macromolecules from three coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2) and their effects on Angiotensin-Converting Enzyme 2 (ACE-2) using computational studies. Based on the identification of the three spike protein macromolecules, it was found that there was a similarity between the active binding sites of ACE-2. These observations were then confirmed using a protein-docking simulation to observe the interaction of the protein spike to the active site of ACE-2. SARS-COV-2 spike protein has the strongest bond to ACE-2, with an ACE score of −1341.85 kJ/mol. Therefore, some of this information from the results of this research can be used as a reference in the development of competitive inhibitor candidates for SARS-CoV-2 spike proteins for the treatment of COVID-19 infectious diseases.

scholarly journals Targeting Virus-Host Interaction: An in Silico Approach to Develop Promising Inhibitors Against COVID-19

2020 ◽  
Author(s):  
Jitendra Subhash Rane ◽  
Aroni Chatterjee ◽  
Rajni Khan ◽  
Abhijeet Kumar ◽  
Shashikant Ray
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Virus Disease ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Host Cell Membrane ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Interaction

The entire human population all over the globe is currently facing appalling conditions due to<br>the spread of infection from COVID-19 (corona virus disease-2019). In the last few months<br>enormous amount of studies have been continuously trying to target several potential drug<br>sites to identify a novel therapeutic target. Spike protein of severe acute respiratory syndrome<br>coronavirus 2 (SARS-CoV-2) is also being targeted by several scientific groups as a novel<br>drug target. The spike glycoprotein protein is present on the surface of the virion and binds to<br>the human angiotensin-converting enzyme-2 (hACE2) membrane receptor thereby promoting<br>its fusion to the host cell membrane. The binding and internalization of the virus is a crucial<br>step in the process of infection and hence any molecule that can inhibit this, certainly holds a<br>significant therapeutic value. We have identified AP-NP (2-(2-amino-5-(naphthalen-2-<br>yl)pyrimidin-4-yl)phenol) and AP-4-Me-Ph (2-(2-amino-5-(p-tolyl)pyrimidin-4-yl)phenol)<br>from a group of diaryl pyrimidine derivatives which appear to bind at the interface of<br>hACE2-SARS-CoV-2S complex (human angiotensin converting enzyme 2 and spike<br>glycoprotein complex) with a low binding energy (<-8 Kcal/mol). In this in-silico study we<br>also found that AP-NP interacts with S1 domain of C-terminal part of SARS-CoV-2S<br>however AP-4-Me-Ph was found to interact with S2 domain of SARS-CoV-2S. The result<br>suggested that AP-NP and AP-4-Me-Ph have potential to inhibit the interaction between<br>spike protein and hACE2 receptor also AP-4-Me-Ph might be prevent internalization of the<br>virion within the host. Further in vitro and in vivo study will strengthen these drug candidates<br>against the COVID-19. <br>

scholarly journals Coronavirus 2019 Infection in People with Associated Co-Morbidities: Case Fatality and ACE2 Inhibitors Treatment Concerns

2020 ◽  
Author(s):  
Maryam Honardoost ◽  
Rokhsareh Aghili ◽  
Mohammad E. Khamseh
Keyword(s):  
Virus Disease ◽  
Case Fatality ◽  
Spike Protein ◽  
Structural Proteins ◽  
Treatment Modalities ◽  
Potential Treatment ◽  
Converting Enzyme ◽  
Therapeutic Approaches ◽  
Angiotensin Converting Enzyme 2 ◽  
Main Target

The Corona Virus Disease 2019 (COVID-19) outbreak is becoming pandemic with the highest mortality in people with associated comorbidities. These RNA viruses containing four structural proteins usually use spike protein to enter the host cell. It has been demonstrated that Angiotensin Converting Enzyme 2 (ACE2) ,as a part of renin-angiotensin-aldosterone system (RAAS), acts as a host receptor for the virus which is the main target of therapeutic approaches. However, medications acting on RAAS can lead to serious complications especially in people with diabetes and hypertension. To avoid this, other potential treatment modalities should be used in COVID-19 patients with associated comorbidities.

scholarly journals Targeting Virus-Host Interaction: An in Silico Approach to Develop Promising Inhibitors Against COVID-19

2020 ◽  
Author(s):  
Jitendra Subhash Rane ◽  
Aroni Chatterjee ◽  
Rajni Khan ◽  
Abhijeet Kumar ◽  
Shashikant Ray
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico ◽  
Virus Disease ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Host Cell Membrane ◽  
Angiotensin Converting Enzyme 2 ◽  
Host Interaction

The entire human population all over the globe is currently facing appalling conditions due to<br>the spread of infection from COVID-19 (corona virus disease-2019). In the last few months<br>enormous amount of studies have been continuously trying to target several potential drug<br>sites to identify a novel therapeutic target. Spike protein of severe acute respiratory syndrome<br>coronavirus 2 (SARS-CoV-2) is also being targeted by several scientific groups as a novel<br>drug target. The spike glycoprotein protein is present on the surface of the virion and binds to<br>the human angiotensin-converting enzyme-2 (hACE2) membrane receptor thereby promoting<br>its fusion to the host cell membrane. The binding and internalization of the virus is a crucial<br>step in the process of infection and hence any molecule that can inhibit this, certainly holds a<br>significant therapeutic value. We have identified AP-NP (2-(2-amino-5-(naphthalen-2-<br>yl)pyrimidin-4-yl)phenol) and AP-4-Me-Ph (2-(2-amino-5-(p-tolyl)pyrimidin-4-yl)phenol)<br>from a group of diaryl pyrimidine derivatives which appear to bind at the interface of<br>hACE2-SARS-CoV-2S complex (human angiotensin converting enzyme 2 and spike<br>glycoprotein complex) with a low binding energy (<-8 Kcal/mol). In this in-silico study we<br>also found that AP-NP interacts with S1 domain of C-terminal part of SARS-CoV-2S<br>however AP-4-Me-Ph was found to interact with S2 domain of SARS-CoV-2S. The result<br>suggested that AP-NP and AP-4-Me-Ph have potential to inhibit the interaction between<br>spike protein and hACE2 receptor also AP-4-Me-Ph might be prevent internalization of the<br>virion within the host. Further in vitro and in vivo study will strengthen these drug candidates<br>against the COVID-19. <br>

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<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>

Preparation and Antitubercular Activities of Palindromic Hydrazinecarbothioamides and Carbonothioic Dihydrazides

2019 ◽  
Vol 16 (11) ◽  
pp. 1202-1210 ◽  
Author(s):  
Michael Joseps Hearn ◽  
Gwendolyn Towers ◽  
Michael Henry Cynamon
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Virulent Strain ◽  
Chemotherapeutic Agents ◽  
Disc Diffusion ◽  
Global Public Health ◽  
Health Crisis ◽  
Chemical Structures ◽  
Public Health Crisis ◽  
Zones Of Inhibition ◽  
Diffusion Assay

Background:With approximately one-third of the world’s population infected, tuberculosis continues to be a global public health crisis. The rise of strains that are unusually virulent or highly resistant to current drugs is a cause of special concern, prompting research into new classes of compounds, as well as the re-evaluation of known chemotherapeutic agents.Objectives:The antimycobacterial activities associated with some recently-reported thiocarbonyl compounds kindled our interest in the synthesis of substituted hydrazinecarbothioamides (3) and carbonothioic dihydrazides (4), with the aim of investigating their potential in antitubercular drug design and discovery.Methods:In the present study, the title compounds 3 and 4 were prepared by the condensation of hydrazines with isothiocyanates in reactions readily controlled by stoichiometry, temperature and solvent. The compounds were assessed against Mycobacterium bovis BCG in Kirby-Bauer disc diffusion, and minimum inhibitory concentrations were determined against the virulent strain M. tuberculosis Erdman.Results:The chemical structures of these thermally stable compounds were determined by IR, 1HNMR, 13C-NMR, high-resolution mass spectrometry and elemental analysis. In the Kirby-Bauer disc diffusion assay, some of the compounds showed substantial diameters of inhibition against BCG. In some cases, the zones of inhibition were so large that no growth at all was observed on the assay plates. Against M. tuberculosis Erdman, several of the compounds showed significant activities. Compound 3h was the most active, demonstrating a minimum inhibitory concentration of 0.5 µg/mL.Conclusion:We found that the title compounds may be prepared conveniently in excellent purity and good yields. They are readily identified on the basis of their characteristic spectra. Some members of this class showed significant activities against mycobacteria. We conclude that further work will be warranted in exploring the antitubercular properties of these compounds.

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