scholarly journals Functional properties of the spike glycoprotein of the emerging SARS-CoV-2 variant B.1.1.529

2021 ◽  
Author(s):  
Qian Wang ◽  
Saumya Anang ◽  
Sho Iketani ◽  
Yicheng Guo ◽  
Lihong Liu ◽  
...  
Keyword(s):  
Virus Infection ◽  
Functional Properties ◽  
Immune Evasion ◽  
Low Temperatures ◽  
Syncytium Formation ◽  
The Other ◽  
Spike Glycoprotein ◽  
Virus Particles ◽  
Cytopathic Effects

The recently emerged B.1.1.529 (Omicron) SARS-CoV-2 variant has a highly divergent spike (S) glycoprotein. We compared the functional properties of B.1.1.529 S with those of previous globally prevalent SARS-CoV-2 variants, D614G and B.1.617.2. Relative to these variants, B.1.1.529 S exhibits decreased processing, resulting in less efficient syncytium formation and lower S incorporation into virus particles. Nonetheless, B.1.1.529 S supports virus infection equivalently. B.1.1.529 and B.1.617.2 S glycoproteins bind ACE2 with higher affinity than D614G S. The unliganded B.1.1.529 S trimer is less stable at low temperatures than the other SARS-CoV-2 spikes, a property related to spike conformation. Upon ACE2 binding, the B.1.1.529 S trimer sheds S1 at 37 degrees but not at 0 degrees C. B.1.1.529 pseudoviruses are relatively resistant to neutralization by sera from convalescent COVID-19 patients and vaccinees. These properties of the B.1.1.529 spike glycoprotein likely influence the transmission, cytopathic effects and immune evasion of this emerging variant.

scholarly journals Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects

2020 ◽  
Author(s):  
Hanh T. Nguyen ◽  
Shijian Zhang ◽  
Qian Wang ◽  
Saumya Anang ◽  
Jia Wang ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Fusion ◽  
Cleavage Site ◽  
Virus Entry ◽  
Cytoplasmic Tail ◽  
Syncytium Formation ◽  
Spike Glycoprotein ◽  
Furin Cleavage ◽  
Cytopathic Effects ◽  
Furin Cleavage Site

SARS-CoV-2, a betacoronavirus, is the cause of the COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein trimer mediates virus entry into host cells and cytopathic effects (syncytium formation). We studied the contribution of several S glycoprotein features to these functions, focusing on those that differ among related coronaviruses. Acquisition of the furin cleavage site by the SARS-CoV-2 S glycoprotein decreased virus stability and infectivity, but greatly enhanced syncytium-forming ability. Notably, the D614G change found in globally predominant SARS-CoV-2 strains increased infectivity, modestly enhanced responsiveness to the ACE2 receptor and susceptibility to neutralizing sera, and tightened association of the S1 subunit with the trimer. Apparently, these two features of the SARS-CoV-2 S glycoprotein, the furin cleavage site and D614G, have evolved to balance virus infectivity, stability, cytopathicity and antibody vulnerability. Although the endodomain (cytoplasmic tail) of the S2 subunit was not absolutely required for virus entry or syncytium formation, alteration of palmitoylated cysteine residues in the cytoplasmic tail decreased the efficiency of these processes. As proteolytic cleavage contributes to the activation of the SARS-CoV-2 S glycoprotein, we evaluated the ability of protease inhibitors to suppress S glycoprotein function. Matrix metalloprotease inhibitors suppressed S-mediated cell-cell fusion, but not virus entry. Synergy between inhibitors of matrix metalloproteases and TMPRSS2 suggests that both host proteases can activate the S glycoprotein during the process of syncytium formation. These results provide insights into SARS-CoV-2 S glycoprotein-host cell interactions that likely contribute to the transmission and pathogenicity of this pandemic agent. IMPORTANCE The development of an effective and durable SARS-CoV-2 vaccine is essential for combating the growing COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein is the main target of neutralizing antibodies elicited during virus infection or following vaccination. Knowledge of the spike glycoprotein evolution, function and interactions with host factors will help researchers to develop effective vaccine immunogens and treatments. Here we identify key features of the spike glycoprotein, including the furin cleavage site and the D614G natural mutation, that modulate viral cytopathic effects, infectivity and sensitivity to inhibition. We also identify two inhibitors of host metalloproteases that block S-mediated cell-cell fusion, a process that contributes to the destruction of the virus-infected cell.

Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects

2020 ◽  
Author(s):  
Hanh T. Nguyen ◽  
Shijian Zhang ◽  
Qian Wang ◽  
Saumya Anang ◽  
Jia Wang ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Fusion ◽  
Cleavage Site ◽  
Virus Entry ◽  
Cytoplasmic Tail ◽  
Syncytium Formation ◽  
Spike Glycoprotein ◽  
Furin Cleavage ◽  
Cytopathic Effects ◽  
Furin Cleavage Site

ABSTRACTSARS-CoV-2, a betacoronavirus, is the cause of the COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein trimer mediates virus entry into host cells and cytopathic effects. We studied the contribution of several S glycoprotein features to these functions, focusing on those that differ among related coronaviruses. Acquisition of the furin cleavage site by the SARS-CoV-2 S glycoprotein decreased virus stability and infectivity, but greatly enhanced the ability to form lethal syncytia. Notably, the D614G change found in globally predominant SARS-CoV-2 strains restored infectivity, modestly enhanced responsiveness to the ACE2 receptor and susceptibility to neutralizing sera, and tightened association of the S1 subunit with the trimer. Apparently, two unique features of the SARS-CoV-2 S glycoprotein, the furin cleavage site and D614G, have evolved to balance virus infectivity, stability, cytopathicity and antibody vulnerability. Although the endodomain (cytoplasmic tail) of the S2 subunit was not absolutely required for virus entry or syncytium formation, alteration of palmitoylated cysteine residues in the cytoplasmic tail decreased the efficiency of these processes. As proteolytic cleavage contributes to the activation of the SARS-CoV-2 S glycoprotein, we evaluated the ability of protease inhibitors to suppress S glycoprotein function. Matrix metalloprotease inhibitors suppressed S-mediated cell-cell fusion, but not virus entry. Synergy between inhibitors of matrix metalloproteases and TMPRSS2 suggests that both proteases can activate the S glycoprotein during the process of syncytium formation. These results provide insights into SARS-CoV-2 S glycoprotein-host cell interactions that likely contribute to the transmission and pathogenicity of this pandemic agent.IMPORTANCEThe development of an effective and durable SARS-CoV-2 vaccine is essential for combating the growing COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein is the main target of neutralizing antibodies elicited during virus infection or following vaccination. Knowledge of the spike glycoprotein evolution, function and interactions with host factors will help researchers to develop effective vaccine immunogens and treatments. Here we identify key features of the spike glycoprotein, including the furin cleavage site and the D614G natural mutation, that modulate viral cytopathic effects, infectivity and sensitivity to inhibition. We also identify two inhibitors of host metalloproteases that block S-mediated cell-cell fusion, which contributes to the destruction of the virus-infected cell.

scholarly journals Catalytic Conversion of n-C7 Asphaltenes and Resins II into Hydrogen Using CeO2-Based Nanocatalysts

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1301
Author(s):  
Oscar E. Medina ◽  
Jaime Gallego ◽  
Sócrates Acevedo ◽  
Masoud Riazi ◽  
Raúl Ocampo-Pérez ◽  
...  
Keyword(s):  
Hydrogen Production ◽  
Low Temperatures ◽  
Gaseous Mixture ◽  
H2 Production ◽  
The Other ◽  
Hydrogen Release ◽  
Catalytic Gasification ◽  
Three Samples ◽  
Main Decomposition ◽  
Catalytic Capacity

This study focuses on evaluating the volumetric hydrogen content in the gaseous mixture released from the steam catalytic gasification of n-C7 asphaltenes and resins II at low temperatures (<230 °C). For this purpose, four nanocatalysts were selected: CeO2, CeO2 functionalized with Ni-Pd, Fe-Pd, and Co-Pd. The catalytic capacity was measured by non-isothermal (from 100 to 600 °C) and isothermal (220 °C) thermogravimetric analyses. The samples show the main decomposition peak between 200 and 230 °C for bi-elemental nanocatalysts and 300 °C for the CeO2 support, leading to reductions up to 50% in comparison with the samples in the absence of nanoparticles. At 220 °C, the conversion of both fractions increases in the order CeO2 < Fe-Pd < Co-Pd < Ni-Pd. Hydrogen release was quantified for the isothermal tests. The hydrogen production agrees with each material’s catalytic activity for decomposing both fractions at the evaluated conditions. CeNi1Pd1 showed the highest performance among the other three samples and led to the highest hydrogen production in the effluent gas with values of ~44 vol%. When the samples were heated at higher temperatures (i.e., 230 °C), H2 production increased up to 55 vol% during catalyzed n-C7 asphaltene and resin conversion, indicating an increase of up to 70% in comparison with the non-catalyzed systems at the same temperature conditions.

scholarly journals Are RNA-Based Tests Sufficient for COVID-19 Diagnosis? An Inspiration of Three Asymptomatic Cases

2021 ◽  
Vol 30 ◽  
pp. 096368972098545
Author(s):  
Tao Hu ◽  
Xiao Liu ◽  
Qinan Yin ◽  
Xingting Duan ◽  
Li Yan
Keyword(s):  
Computed Tomography ◽  
Nucleic Acid ◽  
Virus Infection ◽  
Severe Acute Respiratory Syndrome ◽  
The Other ◽  
Computed Tomography Scan ◽  
Health Authorities ◽  
History Of ◽  
Tomography Scan ◽  
Nucleic Acid Tests

In this work, we discovered a new phenomenon—asymptomatic COVID-19 infection, or covert case, during the pandemic. All the 3 patients had a history of exposure, with no symptoms, and no abnormalities were found in computed tomography scan or lab tests. Except for case 2, the other patients’ severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) nucleic acid tests were negative. But their anti-SARS-COV-2 nucleocapsid antibody showed a dynamic trend, consistent with the process of virus infection and clearance. A growing number of asymptomatic or covert cases need more attention. Lack of surveillance may lead to another outbreak. We hope to demonstrate our cases to attract the attention of governments or health authorities that covert cases should be the focus as well.

Interaction Between Low Temperatures Spacers and Source Drain Extensions and Pockets for Both NMOS and PMOS of the 65 nm Node Technology

2006 ◽  
Vol 912 ◽  
Author(s):  
Nathalie Cagnat ◽  
Cyrille Laviron ◽  
Daniel Mathiot ◽  
Pierre Morin ◽  
Frédéric Salvetti ◽  
...  
Keyword(s):  
Oxide Layer ◽  
Hydrogen Content ◽  
Low Temperatures ◽  
Direct Contact ◽  
Fabrication Process ◽  
Experimental Results ◽  
The Other ◽  
Mos Transistors ◽  
Phosphorus Source ◽  
Activation Annealing

AbstractDuring the MOS transistors fabrication process, the source-drain extension areas are directly in contact with the oxide liner of the spacers stack. In previous works [1, 2, 3] it has been established that boron can diffuse from the source-drain extensions into the spacer oxide liner during the subsequent annealing steps, and that the amount of boron loss depends on the hydrogen content in the oxide, because it enhances B diffusivity in SiO2.In order to characterize and quantify the above phenomena, we performed test experiments on full sheet samples, which mimic either BF2 source-drain extensions over arsenic pockets implants, or BF2 pockets under arsenic or phosphorus source-drain extensions implants. Following the corresponding implants, the wafers were covered with different spacer stacks (oxide + nitride) deposited either by LPCVD, or PECVD. After appropriate activation annealing steps, SIMS measurements were used to characterize the profiles of the various dopants, and the corresponding dose loss was evaluated for each species.Our experimental results clearly evidence that LPCVD or PECVD spacer stacks have no influence on the arsenic profiles. On the other hand, phosphorus and boron profiles are affected. For boron profiles, each spacer type has a different influence. It is also shown that boron out-diffuses not only from the B doped source-drain extension in direct contact with the oxide layer, but also from the "buried" B pockets lying under n-doped source drain extension areas. All these results are discussed in term of the possible relevant mechanism.

scholarly journals Verbal Monomials in English for Audit and Accounting

2021 ◽  
Vol 04 (03) ◽  
Author(s):  
Oksana Chaika ◽  
Keyword(s):  
Functional Properties ◽  
Functional Property ◽  
The Other ◽  
Discussion Section ◽  
Work In Progress ◽  
The One

The paper research is work in progress and makes part of a publication set devoted the study of the English monomials and polynomials in the professional domain of audit and accounting, on the one hand. On the other, the research can be treated as a standalone piece for the study into the nature of verbal monomials as set term clusters in English for Audit and Accounting. The scope of research arrives at the following objectives. One objective is to give an overview of the term ‘monomial’ in English for Audit and Accounting, or English for A&A, which leads to understanding of the verbal monomial in English for A&A, correspondingly. The other objective refers to the classification introduced earlier as attributable to the analysis of the structure of the mentioned monomials and polynomials in English for A&A from a morphological perspective of the head term in a monomial, i.e. nounal, verbal, adjectival and adverbial. The said classification in this work associates with verbal monomials in English for A&A only, and provides a relevant sub-classification of the relevant verbal monomials through the lens of their functional properties and roles in a sentence, under the professional language framework. The results and discussion section presents five distinct groups of verbal monomials in English for Audit and Accounting, each corresponding to a specific syntactical role and functional property in a sentence. A variety of the examples helps see and identify the type of the English verbal monomial in the area of audit and accounting.

scholarly journals The principal magnetic susceptibilities of neodymium sulphate octahydrate at low temperatures

1939 ◽  
Vol 170 (941) ◽  
pp. 266-271 ◽  
Keyword(s):  
Low Temperatures ◽  
Room Temperature ◽  
Energy Levels ◽  
Constant Factor ◽  
The Other ◽  
Crystalline Field ◽  
Cubic Symmetry ◽  
The Subject ◽  
The Difference ◽  
The One

The magnetic and other related properties of neodymium sulphate have been the subject of numerous investigations in recent years, but there is still a remarkable conflict of evidence on all the essential points. The two available determinations of the susceptibility of the powdered salt at low temperatures, those of Gorter and de Haas (1931) from 290 to 14° K and of Selwood (1933) from 343 to 83° K both fit the expression X ( T + 45) = constant over the range of temperature common to both, but the constants are not the same and the susceptibilities at room temperature differ by 11%. The fact that the two sets of results can be converted the one into the other by multiplying throughout by a constant factor suggested that the difference in the observed susceptibilities was due to some error of calibration. It could, however, also be due to the different purity of the samples examined though the explanation of the occurrence of the constant factor is then by no means obvious. From their analysis of the absorption spectrum of crystals of neodymium sulphate octahydrate Spedding and others (1937) conclude that the crystalline field around the Nd+++ ion is predominantly cubic in character since they find three energy levels at 0, 77 and 260 cm. -1 .* Calculations of the susceptibility from these levels reproduce Selwood’s value at room temperature but give no agreement with the observations-at other temperatures. On the other hand, Penney and Schlapp (1932) have shown that Gorter and de Haas’s results fit well on the curve calculated for a crystalline field of cubic symmetry and such a strength that the resultant three levels lie at 0, 238 and 834 cm. -1 , an overall spacing almost three times as great as Spedding’s.

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