scholarly journals SARS-CoV-2 Spike-Heat Shock Protein A5 (GRP78) Recognition may be Related to the Immersed Human Coronaviruses

2020 ◽  
Vol 11 ◽  
Author(s):  
Abdo A. Elfiky
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Viral Entry ◽  
Economic Burden ◽  
Experimental Validation ◽  
Recognition Site ◽  
Spike Protein ◽  
Human Coronavirus ◽  
Protein Target ◽  
Human Coronaviruses

The human coronavirus (HCoV), SARS-CoV-2, caused more than 34 M confirmed infections from which more than 1 M deaths are reported until now (the WHO situation report-154). The current pandemic causes severe socio-economic burden. Due to the importance of understanding of the mode of recognition and viral entry, spike protein shed drug designers as the first look protein target with the first released solved structure on 26 February 2020 (PDB ID: 6VSB). It is proposed that the recognition site for GRP78 is found in SARS-CoV-2 and the immersed human coronaviruses but experimental validation is still required.

scholarly journals Human coronavirus dependency on host heat shock protein 90 reveals an antiviral target

2020 ◽  
Vol 9 (1) ◽  
pp. 2663-2672
Author(s):  
Cun Li ◽  
Hin Chu ◽  
Xiaojuan Liu ◽  
Man Chun Chiu ◽  
Xiaoyu Zhao ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Human Coronavirus

scholarly journals Differential Downregulation of ACE2 by the Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63

2009 ◽  
Vol 84 (2) ◽  
pp. 1198-1205 ◽  
Author(s):  
Ilona Glowacka ◽  
Stephanie Bertram ◽  
Petra Herzog ◽  
Susanne Pfefferle ◽  
Imke Steffen ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Lung Injury ◽  
Vero Cells ◽  
Cell Entry ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Human Coronavirus ◽  
Angiotensin Converting Enzyme 2 ◽  
Similar Activity ◽  
Human Coronaviruses

ABSTRACT The human coronaviruses (CoVs) severe acute respiratory syndrome (SARS)-CoV and NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown that recombinant SARS-CoV spike protein (SARS-S) downregulates ACE2 expression and thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet unknown. We found that recombinant SARS-S bound to ACE2 and induced ACE2 shedding with higher efficiency than NL63-S. Shedding most likely accounted for the previously observed ACE2 downregulation but was dispensable for viral replication. Finally, SARS-CoV but not NL63 replicated efficiently in ACE2-positive Vero cells and reduced ACE2 expression, indicating robust receptor interference in the context of SARS-CoV but not NL63 infection.

scholarly journals Differential expression in humans of the viral entry receptor ACE2 compared with the short deltaACE2 isoform lacking SARS-CoV-2 binding sites

2021 ◽  
Author(s):  
Thomas L. Williams ◽  
Gregory Strachan ◽  
Robyn G.C. Macrae ◽  
Rhoda E. Kuc ◽  
Duuamene Nyimanu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Differential Expression ◽  
Viral Entry ◽  
Binding Sites ◽  
Spike Protein ◽  
Natural Resistance ◽  
Cell Infection ◽  
Antibody Staining ◽  
Human Coronaviruses ◽  
Entry Receptor

Abstract ACE2 is a membrane protein that regulates the cardiovascular system. Additionally, ACE2 acts as a receptor for host cell infection by human coronaviruses, including SARS-CoV-2 that emerged as the cause of the on-going COVID-19 pandemic and has brought unprecedented burden to economy and health. ACE2 binds the spike protein of SARS-CoV-2 with high affinity and shows little variation in amino acid sequence meaning natural resistance is rare. The discovery of a novel short ACE2 isoform (deltaACE2) provides evidence for inter-individual differences in SARS-CoV-2 susceptibility and severity, and likelihood of developing subsequent ‘Long COVID’. Critically, deltaACE2 loses SARS-CoV-2 spike protein binding sites in the extracellular domain, and is predicted to confer reduced susceptibility to viral infection. We aimed to assess the differential expression of full-length ACE2 versus deltaACE2 in a panel of human tissues (kidney, heart, lung, and liver) that are implicated in COVID-19, and confirm ACE2 protein in these tissues. Using dual antibody staining, we show that deltaACE2 localises, and is enriched, in lung airway epithelia and bile duct epithelia in the liver. Finally, we also confirm that a fluorescently tagged SARS-CoV-2 spike protein monomer shows low binding at lung and bile duct epithelia where dACE2 is enriched.

scholarly journals Human Coronavirus HKU1 Spike Protein UsesO-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme

2015 ◽  
Vol 89 (14) ◽  
pp. 7202-7213 ◽  
Author(s):  
Xingchuan Huang ◽  
Wenjuan Dong ◽  
Aleksandra Milewska ◽  
Anna Golda ◽  
Yonghe Qi ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Viral Entry ◽  
Host Cells ◽  
Cellular Receptor ◽  
Respiratory Pathogens ◽  
Airway Epithelial ◽  
Human Coronavirus ◽  
Rd Cells ◽  
Human Coronaviruses

ABSTRACTHuman coronavirus (hCoV) HKU1 is one of six hCoVs identified to date and the only one with an unidentified cellular receptor. hCoV-HKU1 encodes a hemagglutinin-esterase (HE) protein that is unique to the group a betacoronaviruses (group 2a). The function of HKU1-HE remains largely undetermined. In this study, we examined binding of the S1 domain of hCoV-HKU1 spike to a panel of cells and found that the S1 could specifically bind on the cell surface of a human rhabdomyosarcoma cell line, RD. Pretreatment of RD cells with neuraminidase (NA) and trypsin greatly reduced the binding, suggesting that the binding was mediated by sialic acids on glycoproteins. However, unlike other group 2a CoVs, e.g., hCoV-OC43, for which 9-O-acetylated sialic acid (9-O-Ac-Sia) serves as a receptor determinant, HKU1-S1 bound with neither 9-O-Ac-Sia-containing glycoprotein(s) nor rat and mouse erythrocytes. Nonetheless, the HKU1-HE was similar to OC43-HE, also possessed sialate-O-acetylesterase activity, and acted as a receptor-destroying enzyme (RDE) capable of eliminating the binding of HKU1-S1 to RD cells, whereas theO-acetylesterase-inactive HKU1-HE mutant lost this capacity. Using primary human ciliated airway epithelial (HAE) cell cultures, the onlyin vitroreplication model for hCoV-HKU1 infection, we confirmed that pretreatment of HAE cells with HE but not the enzymatically inactive mutant blocked hCoV-HKU1 infection. These results demonstrate that hCoV-HKU1 exploitsO-Ac-Sia as a cellular attachment receptor determinant to initiate the infection of host cells and that its HE protein possesses the corresponding sialate-O-acetylesterase RDE activity.IMPORTANCEHuman coronaviruses (hCoV) are important human respiratory pathogens. Among the six hCoVs identified to date, only hCoV-HKU1 has no defined cellular receptor. It is also unclear whether hemagglutinin-esterase (HE) protein plays a role in viral entry. In this study, we found that, similarly to other members of the group 2a CoVs, sialic acid moieties on glycoproteins are critical receptor determinants for the hCoV-HKU1 infection. Interestingly, the virus seems to employ a type of sialic acid different from those employed by other group 2a CoVs. In addition, we determined that the HKU1-HE protein is anO-acetylesterase and acts as a receptor-destroying enzyme (RDE) for hCoV-HKU1. This is the first study to demonstrate that hCoV-HKU1 uses certain types ofO-acetylated sialic acid residues on glycoproteins to initiate the infection of host cells and that the HKU1-HE protein possesses sialate-O-acetylesterase RDE activity.

scholarly journals Specific serology for emerging human coronaviruses by protein microarray

2013 ◽  
Vol 18 (14) ◽  
Author(s):  
C Reusken ◽  
H Mou ◽  
G J Godeke ◽  
L van der Hoek ◽  
B Meyer ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Protein Microarray ◽  
Spike Protein ◽  
Microarray Technology ◽  
Igg Antibodies ◽  
Specific Detection ◽  
Human Coronavirus ◽  
Serological Assay ◽  
Human Coronaviruses ◽  
Binding Subunit

We present a serological assay for the specific detection of IgM and IgG antibodies against the emerging human coronavirus hCoV-EMC and the SARS-CoV based on protein microarray technology. The assay uses the S1 receptor-binding subunit of the spike protein of hCoV-EMC and SARS-CoV as antigens. The assay has been validated extensively using putative cross-reacting sera of patient cohorts exposed to the four common hCoVs and sera from convalescent patients infected with hCoV-EMC or SARS-CoV.

scholarly journals Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies

2020 ◽  
Author(s):  
Scott M. Matushek ◽  
Kathleen G. Beavis ◽  
Ana Abeleda ◽  
Cindy Bethel ◽  
Carlissa Hunt ◽  
...  
Keyword(s):  
Clinical Microbiology ◽  
Spike Protein ◽  
Quantitative Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Elisa Assay ◽  
Plasma Samples ◽  
Igg Antibodies ◽  
Human Coronavirus ◽  
Human Coronaviruses ◽  
The University

AbstractAs the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 57 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 53 tested negative and 4 tested positive for IgA (93.0% agreement) while 56 tested negative and 1 tested positive for IgG (98.2% agreement). For COVID-19 PCR-positive patients, 29 of 30 (96.7%) samples collected ≥3 days after positive PCR were positive for IgA, and 28 of 28 samples collected ≥4 days after positive PCR were positive for IgG.The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrates excellent sensitivity for detection of IgA and IgG antibodies from samples collected ≥3 days and ≥4 days, respectively, after COVID-19 diagnosis by PCR. This assay did not demonstrate cross reaction in any of the 28 samples from patients with common human coronaviruses, including types HKU1, NL63, CV229E, and OC43.

scholarly journals Differential expression in humans of the viral entry receptor ACE2 compared with the short deltaACE2 isoform lacking SARS-CoV-2 binding sites

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas L. Williams ◽  
Gregory Strachan ◽  
Robyn G. C. Macrae ◽  
Rhoda E. Kuc ◽  
Duuamene Nyimanu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Differential Expression ◽  
Viral Entry ◽  
Binding Sites ◽  
Spike Protein ◽  
Natural Resistance ◽  
Cell Infection ◽  
Antibody Staining ◽  
Human Coronaviruses ◽  
Entry Receptor

AbstractACE2 is a membrane protein that regulates the cardiovascular system. Additionally, ACE2 acts as a receptor for host cell infection by human coronaviruses, including SARS-CoV-2 that emerged as the cause of the on-going COVID-19 pandemic and has brought unprecedented burden to economy and health. ACE2 binds the spike protein of SARS-CoV-2 with high affinity and shows little variation in amino acid sequence meaning natural resistance is rare. The discovery of a novel short ACE2 isoform (deltaACE2) provides evidence for inter-individual differences in SARS-CoV-2 susceptibility and severity, and likelihood of developing subsequent ‘Long COVID’. Critically, deltaACE2 loses SARS-CoV-2 spike protein binding sites in the extracellular domain, and is predicted to confer reduced susceptibility to viral infection. We aimed to assess the differential expression of full-length ACE2 versus deltaACE2 in a panel of human tissues (kidney, heart, lung, and liver) that are implicated in COVID-19, and confirm ACE2 protein in these tissues. Using dual antibody staining, we show that deltaACE2 localises, and is enriched, in lung airway epithelia and bile duct epithelia in the liver. Finally, we also confirm that a fluorescently tagged SARS-CoV-2 spike protein monomer shows low binding at lung and bile duct epithelia where dACE2 is enriched.

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