scholarly journals An Evaluation of the Potential of Heparin to Inhibit the Viral Entry of SARS-CoV-2

2021 ◽  
Keyword(s):  
Viral Entry ◽  
The Body ◽  
Ligand Docking ◽  
Binding Potential ◽  
Docking Simulations ◽  
Binding Domains ◽  
Wide Range ◽  
Novel Coronavirus ◽  
Viral Components ◽  
High Degree

Heparin is an anticoagulant medicine that prevents the formation of harmful blood clots in the vessels. Following the outbreak of the novel coronavirus disease 2019 (COVID-19), heparin has helped to improve the health of affected patients beyond its anticoagulant effects. The potential antiviral activity of heparin has attracted speculation due to its highly sulfated profile, which allows it to have a high binding affinity to a wide range of viral components. Heparin’s successful binding to the ZIKA virus, human immunodeficiency virus, as well as the SARS CoV and MERS CoV spike proteins have demonstrated its potential to inhibit the entry of SARS-CoV-2 into the body. A high degree of sequence homology also enables heparin to have inhibitory binding potential on viral components. The SARS-CoV-2 virus exhibits significant differences in its spike glycoprotein (SGP) sequence compared to other coronaviruses. The SGP sequence in SARS-CoV-2 contains additional potential glycosaminoglycan (GAG) binding domains that may drive differences in the attachment and entry process of the virus. Findings from unbiased computational ligand docking simulations, pseudotyped spike protein experiments, and cell to cell fusion assays have also opened possibilities to investigate the antiviral properties of heparin in clinical trials

scholarly journals Large elastic deformations of isotropic materials. I. Fundamental concepts

1948 ◽  
Vol 240 (822) ◽  
pp. 459-490 ◽  
Keyword(s):  
The Body ◽  
Elastic Behaviour ◽  
Stress And Strain ◽  
Elastic Deformations ◽  
Hooke’S Law ◽  
Widespread Agreement ◽  
Wide Range ◽  
Hooke's Law ◽  
High Degree

The mathematical theory of small elastic deformations has been developed to a high degree of sophistication on certain fundamental assumptions regarding the stress-strain relationships which are obeyed by the materials considered. The relationships taken are, in effect, a generalization of Hooke’s law— ut tensio, sic vis . The justification for these assumptions lies in the widespread agreement of experiment with the predictions of the theory and in the interpretation of the elastic behaviour of the materials in terms of their known structure. The same factors have contributed to our appreciation of the limitations of these assumptions. The principal problems, which the theory seeks to solve, are the determination of the deformation which a body undergoes and the distribution of stresses in it, when certain forces are applied to it, and when certain points of the body are subjected to specified displacements. These problems are always dealt with on the assumption that the generalization of Hooke’s law is obeyed by the material of the body and that the deformation is small, i.e. the change of length, in any linear element in the material, is small compared with the length of the element in the undeformed state. Apart from the fact that the generalization of Hooke’s law is obeyed accurately by a very wide range of materials, under a considerable variety of stress and strain conditions, it has the further advantage that it leads to a mathematically tractable theory.

scholarly journals Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein

2020 ◽  
Author(s):  
Alexandra C. Walls ◽  
Young-Jun Park ◽  
M. Alexandra Tortorici ◽  
Abigail Wall ◽  
Andrew T. McGuire ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Target Cells ◽  
Furin Cleavage ◽  
Humoral Immune ◽  
Binding Domains ◽  
Furin Cleavage Site ◽  
Recent Emergence ◽  
Novel Coronavirus

SUMMARYThe recent emergence of a novel coronavirus associated with an ongoing outbreak of pneumonia (Covid-2019) resulted in infections of more than 72,000 people and claimed over 1,800 lives. Coronavirus spike (S) glycoprotein trimers promote entry into cells and are the main target of the humoral immune response. We show here that SARS-CoV-2 S mediates entry in VeroE6 cells and in BHK cells transiently transfected with human ACE2, establishing ACE2 as a functional receptor for this novel coronavirus. We further demonstrate that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, which correlates with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and other SARS-related CoVs. We determined a cryo-electron microscopy structure of the SARS-CoV-2 S ectodomain trimer, demonstrating spontaneous opening of the receptor-binding domain, and providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal sera potently inhibited SARS-CoV-2 S-mediated entry into target cells, thereby indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

scholarly journals Potential host range of multiple SARS-like coronaviruses and an improved ACE2-Fc variant that is potent against both SARS-CoV-2 and SARS-CoV-1

2020 ◽  
Author(s):  
Yujun Li ◽  
Haimin Wang ◽  
Xiaojuan Tang ◽  
Danting Ma ◽  
Chengzhi Du ◽  
...  
Keyword(s):  
Host Range ◽  
Viral Entry ◽  
Intermediate Hosts ◽  
Domestic Species ◽  
Entry Inhibitors ◽  
Binding Domains ◽  
Protein Receptor ◽  
Wide Range ◽  
Bat Coronavirus ◽  
Insight Into

SUMMARYThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a currently uncontrolled pandemic and the etiological agent of coronavirus disease 2019 (COVID-19). It is important to study the host range of SARS-CoV-2 because some domestic species might harbor the virus and transmit it back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. Here we show that ACE2 orthologs of a wide range of domestic and wild animals support entry of SARS-CoV-2, as well as that of SARS-CoV-1, bat coronavirus RaTG13, and a coronavirus isolated from pangolins. Some of these species, including camels, cattle, horses, goats, sheep, pigs, cats, and rabbits may serve as potential intermediate hosts for new human transmission, and rabbits in particular may serve as a useful experimental model of COVID-19. We show that SARS-CoV-2 and SARS-CoV-1 entry could be potently blocked by recombinant IgG Fc-fusion proteins of viral spike protein receptor-binding domains (RBD-Fc) and soluble ACE2 (ACE2-Fc). Moreover, an ACE2-Fc variant, which carries a D30E mutation and has ACE2 truncated at its residue 740 but not 615, outperforms all the other ACE2-Fc variants on blocking entry of both viruses. Our data suggest that RBD-Fc and ACE2-Fc could be used to treat and prevent infection of SARS-CoV-2 and any new viral variants that emerge over the course of the pandemic.

scholarly journals The average energy of disintegration of radium E

1927 ◽  
Vol 117 (776) ◽  
pp. 109-123 ◽  
Keyword(s):  
Average Energy ◽  
The Body ◽  
Secondary Process ◽  
Characteristic Energy ◽  
Γ Radiation ◽  
Wide Range ◽  
Continuous Energy Spectrum ◽  
The Mean ◽  
High Degree ◽  
Α Particles

The problem of the velocity of the particles emitted from the nuclei of dis integrating radioactive atoms has always attracted considerable attention. It was early established that in the case of the α-rays all the particles from one substance were emitted with the same velocity, and the latest experiments of Briggs have emphasised the high degree of homogeneity attained. This result, showing that each disintegration involves exactly the same emission of energy, is easily reconcilable with our general ideas of the radioactive processes, and, as is well known, there is undoubtedly some connection between this characteristic energy and the mean life of the body. The behaviour of the β-ray bodies is in sharp contrast to this. In place of the α-particles all emitted with the same energy, we find that the disintegration electrons coming from the nucleus have energies distributed over a wide range. For example, in the case of radium E this continuous energy spectrum formed by the disintegration electrons has an upper limit at 1,050,000 volts, rises to a maximum at 300,000 volts, and continues certainly as low as 40,000 volts, and similar results have been obtained for other β-ray bodies. If this result is interpreted as showing that different disintegrating nuclei of the same substance emit their disintegration electron with different energies, we must deduce that in this case the energy of disintegration is not a characteristic constant of the body, but can vary between wide limits. Many workers have considered this to be so contrary both to the ideas of the quantum theory and the definiteness shown by radioactive disintegration that they have asserted the inhomogeneity must be a result of some secondary process, such as collision with the extranuclear electrons or emission of general γ-radiation, and that although we cannot observe them before they become inhomogeneous, the disintegration electrons are actually emitted from the nucleus with a definite characteristic energy as in the case of the α-particles.

scholarly journals Immune Response towards COVID-19

2021 ◽  
Vol 2 (12) ◽  
pp. 1197-1201
Author(s):  
Muhammad Akram ◽  
Waqas Ahmed ◽  
Abolfazl Jafari-Sales ◽  
Nilgun Kusculu ◽  
Mounir M Bekhit ◽  
...  
Keyword(s):  
Immune Response ◽  
The Body ◽  
Elastic Response ◽  
Lung Cells ◽  
Angiotensin Converting Enzyme 2 ◽  
Non Invasive ◽  
Natural Response ◽  
Novel Coronavirus ◽  
Viral Components ◽  
Source Retrieval

Background: As the world witnessed the outbreak of coronavirus illness 2019 (COVID-19), a disorder developed as a result of a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), increasing genetics with healthcare evidence suggest a corresponding leadership to SARS as well as the Middle East Respiratory Syndrome (MERS). Aim: The aim of this review is to highlight Immune response of human body toward COVID-19. Materials and methods: This was a narrative review. A comprehensive literature search was done using PubMed, Google Scholar, Scopus, and EMBASE using the keywords, Immune Response; COVID-19; Vaccination; SARS-Cov-2; ACE2; Coronavirus; MERS. Results: A flow of viral components passes to the body by means of nostrils, mouth and eyes. SARS-CoV-2 is in a position to continue to become unnoticed extended than numerous influenza or coronaviruses. Its proteins can accomplish entry by unlocking the Angiotensin-Converting Enzyme 2 (ACE2) protein in the lung cells; viruses also possess antigens furthermore recognize that these are what cries the immunity into movement via making antibodies. Investigators demonstrate an extensive variety of immune cells respond to COVID-19 along with valuable source retrieval, discovering that might want to notify the manufacturing of a viable vaccination. Conclusion: The body's natural response to a viral infection is a non-invasive intrinsic response in which macrophages, neutrophils, and dendritic cells limit the virus's progression and may even prevent it by multiplying symptoms. This non-invasive solution is accompanied by an elastic response in which the body produces radicals that primarily adjust to the herpes virus.

Creating the Wind

2020 ◽  
Vol 2 (4) ◽  
pp. 14-31
Author(s):  
Élodie Dupey García
Keyword(s):  
Indigenous Communities ◽  
The Body ◽  
Historical Sources ◽  
Natural Behavior ◽  
Sensory Experiences ◽  
Identity And Agency ◽  
Wide Range ◽  
Late Postclassic ◽  
Comparative Examination ◽  
Meteorological Phenomenon

This article explores how the Nahua of late Postclassic Mesoamerica (1200–1521 CE) created living and material embodiments of their wind god constructed on the basis of sensory experiences that shaped their conception of this divinized meteorological phenomenon. In this process, they employed chromatic and design devices, based on a wide range of natural elements, to add several layers of meaning to the human, painted, and sculpted supports dressed in the god’s insignia. Through a comparative examination of pre-Columbian visual production—especially codices and sculptures—historical sources mainly written in Nahuatl during the viceregal period, and ethnographic data on indigenous communities in modern Mexico, my analysis targets the body paint and shell jewelry of the anthropomorphic “images” of the wind god, along with the Feathered Serpent and the monkey-inspired embodiments of the deity. This study identifies the centrality of other human senses beyond sight in the conception of the wind god and the making of its earthly manifestations. Constructing these deity “images” was tantamount to creating the wind because they were intended to be visual replicas of the wind’s natural behavior. At the same time, they referred to the identity and agency of the wind god in myths and rituals.

Understanding Conformational Entropy in Small Molecules

2020 ◽  
Author(s):  
Lucian Chan ◽  
Garrett Morris ◽  
Geoffrey Hutchison
Keyword(s):  
Small Molecules ◽  
Degrees Of Freedom ◽  
Absolute Error ◽  
Low Energy ◽  
Standard Entropy ◽  
Free Energies ◽  
Conformational Entropy ◽  
Wide Range ◽  
High Degree ◽  
Empirical Corrections

The calculation of the entropy of flexible molecules can be challenging, since the number of possible conformers grows exponentially with molecule size and many low-energy conformers may be thermally accessible. Different methods have been proposed to approximate the contribution of conformational entropy to the molecular standard entropy, including performing thermochemistry calculations with all possible stable conformations, and developing empirical corrections from experimental data. We have performed conformer sampling on over 120,000 small molecules generating some 12 million conformers, to develop models to predict conformational entropy across a wide range of molecules. Using insight into the nature of conformational disorder, our cross-validated physically-motivated statistical model can outperform common machine learning and deep learning methods, with a mean absolute error ≈4.8 J/mol•K, or under 0.4 kcal/mol at 300 K. Beyond predicting molecular entropies and free energies, the model implies a high degree of correlation between torsions in most molecules, often as- sumed to be independent. While individual dihedral rotations may have low energetic barriers, the shape and chemical functionality of most molecules necessarily correlate their torsional degrees of freedom, and hence restrict the number of low-energy conformations immensely. Our simple models capture these correlations, and advance our understanding of small molecule conformational entropy.

A Potential Role of Coenzyme Q10 Deficiency in Severe SARS-CoV2 Infection

2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Vasilios M. Polymeropoulos ◽  
Keyword(s):  
Viral Entry ◽  
Coenzyme Q10 ◽  
Severe Infection ◽  
The Body ◽  
Therapeutic Options ◽  
Severe Illness ◽  
Infected People ◽  
Inflammatory State ◽  
Exogenous Compounds ◽  
Obesity Hypertension

There is a dramatic need for extensive research into the predictors of severe infection with SARS-CoV2 and therapeutic options for infected people. People who suffer from severe illness and higher mortality display a pattern of having specific co-morbidities (diabetes, obesity, hypertension) and are of higher age. Recent research has described methods of viral entry via receptors (ACE2, TMPRSS2) and the hyper-inflammatory state often associated with severe illness (increase in interleukins, increase in TNF-alpha). These discoveries have led to the research of currently available and developing therapies, that are helpful to patients. Deficiencies of specific vitamins and other endogenous molecules of the body should be examined to understand if a pattern exists among the people most severely affected. Coenzyme Q10 (CoQ10) is a fat-soluble substance ubiquitously expressed throughout the body that is important for the generation of ATP and mediation of inflammatory disease. CoQ10 faces a decline with increasing age, genetic predispositions, and ingestion of exogenous compounds that could reduce the level of CoQ10. Deficiencies and subsequent supplementation with CoQ10 recently has displayed encouraging results for the improvement of a wide variety of diseases. This manuscript is significant as it points to a potential relationship of CoQ10 and the population suffering from severe illness of COVID-19, and further encourages the need for research into measuring the levels of CoQ10 and vitamins to understand if levels predict severe illness and mortality. This could offer new avenues into research in combating this pandemic and potentially future therapeutic options.

Cerebellotrigeminal Dermal Dysplasia (Gómez-López-Hernández Syndrome)

2018 ◽  
Vol 16 (05) ◽  
pp. 362-368 ◽  
Author(s):  
Federica Sullo ◽  
Agata Polizzi ◽  
Stefano Catanzaro ◽  
Selene Mantegna ◽  
Francesco Lacarrubba ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Rearrangements ◽  
Number Of Patients ◽  
Wide Range ◽  
Visual Problems ◽  
Neurodevelopmental Abnormalities ◽  
Clinical Triad ◽  
High Degree ◽  
Motor Handicap

Cerebellotrigeminal dermal (CTD) dysplasia is a rare neurocutaneous disorder characterized by a triad of symptoms: bilateral parieto-occipital alopecia, facial anesthesia in the trigeminal area, and rhombencephalosynapsis (RES), confirmed by cranial magnetic resonance imaging. CTD dysplasia is also known as Gómez-López-Hernández syndrome. So far, only 35 cases have been described with varying symptomatology. The etiology remains unknown. Either spontaneous dominant mutations or de novo chromosomal rearrangements have been proposed as possible explanations. In addition to its clinical triad of RES, parietal alopecia, and trigeminal anesthesia, CTD dysplasia is associated with a wide range of phenotypic and neurodevelopmental abnormalities.Treatment is symptomatic and includes physical rehabilitation, special education, dental care, and ocular protection against self-induced corneal trauma that causes ulcers and, later, corneal opacification. The prognosis is correlated to the mental development, motor handicap, corneal–facial anesthesia, and visual problems. Follow-up on a large number of patients with CTD dysplasia has never been reported and experience is limited to few cases to date. High degree of suspicion in a child presenting with characteristic alopecia and RES has a great importance in diagnosis of this syndrome.

scholarly journals SARS-CoV-2 Is Not Detected in the Cerebrospinal Fluid of Encephalopathic COVID-19 Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Dimitris G. Placantonakis ◽  
Maria Aguero-Rosenfeld ◽  
Abdallah Flaifel ◽  
John Colavito ◽  
Kenneth Inglima ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Viral Entry ◽  
Cell Types ◽  
Host Cells ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Neurologic Sequelae ◽  
Show Evidence ◽  
Novel Coronavirus ◽  
Transmembrane Serine Protease

Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.

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