Cross-Reactive Antibody Against Human Coronavirus OC43 Spike Protein Correlates with Disease Severity in COVID-19 Patients: A Retrospective Study

2020 ◽  
Author(s):  
Li Guo ◽  
Yeming Wang ◽  
Liang Kang ◽  
Yongfeng Hu ◽  
Linghang Wang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Disease Severity ◽  
Spike Protein ◽  
Human Coronavirus ◽  
Reactive Antibody

scholarly journals Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD–ACE2 receptor interaction

2008 ◽  
Vol 89 (4) ◽  
pp. 1015-1024 ◽  
Author(s):  
Han-Xin Lin ◽  
Yan Feng ◽  
Gillian Wong ◽  
Liping Wang ◽  
Bei Li ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Binding Domain ◽  
Site Directed Mutagenesis ◽  
Spike Protein ◽  
Receptor Interaction ◽  
Receptor Binding Domain ◽  
Human Coronavirus ◽  
C Terminus ◽  
Group I ◽  
Truncated Variants

Human coronavirus NL63 (NL63), a member of the group I coronaviruses, may cause acute respiratory diseases in young children and immunocompromised adults. Like severe acute respiratory syndrome coronavirus (SARS-CoV), NL63 also employs the human angiotensin-converting enzyme 2 (hACE2) receptor for cellular entry. To identify residues in the spike protein of NL63 that are important for hACE2 binding, this study first generated a series of S1-truncated variants, examined their associations with the hACE2 receptor and subsequently mapped a minimal receptor-binding domain (RBD) that consisted of 141 residues (aa 476–616) towards the C terminus of the S1 domain. The data also demonstrated that the NL63 RBD bound to hACE2 more efficiently than its full-length counterpart and had a binding efficiency comparable to the S1 or RBD of SARS-CoV. A further series of RBD variants was generated using site-directed mutagenesis and random mutant library screening assays, and identified 15 residues (C497, Y498, V499, C500, K501, R518, R530, V531, G534, G537, D538, S540, E582, W585 and T591) that appeared to be critical for the RBD–hACE2 association. These critical residues clustered in three separate regions (designated RI, RII and RIII) inside the RBD, which may represent three receptor-binding sites. These results may help to delineate the molecular interactions between the S protein of NL63 and the hACE2 receptor, and may also enhance our understanding of the pathogenesis of NL63 and SARS-CoV.

scholarly journals A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody

2020 ◽  
Author(s):  
Nicholas C. Wu ◽  
Meng Yuan ◽  
Sandhya Bangaru ◽  
Deli Huang ◽  
Xueyong Zhu ◽  
...  
Keyword(s):  
Antigenic Variation ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Single Mutation ◽  
X Ray ◽  
X Ray Crystallography ◽  
Negative Stain ◽  
Natural Mutation ◽  
Reactive Antibody ◽  
Conserved Epitope

ABSTRACTEpitopes that are conserved among SARS-like coronaviruses are attractive targets for design of cross-reactive vaccines and therapeutics. CR3022 is a SARS-CoV neutralizing antibody to a highly conserved epitope on the receptor binding domain (RBD) on the spike protein that can cross-react with SARS-CoV-2, but with lower affinity. Using x-ray crystallography, mutagenesis, and binding experiments, we illustrate that of four amino acid differences in the CR3022 epitope between SARS-CoV-2 and SARS-CoV, a single mutation P384A fully determines the affinity difference. CR3022 does not neutralize SARS-CoV-2, but the increased affinity to SARS-CoV-2 P384A mutant now enables neutralization with a similar potency to SARS-CoV. We further investigated CR3022 interaction with the SARS-CoV spike protein by negative-stain EM and cryo-EM. Three CR3022 Fabs bind per trimer with the RBD observed in different up-conformations due to considerable flexibility of the RBD. In one of these conformations, quaternary interactions are made by CR3022 to the N-terminal domain (NTD) of an adjacent subunit. Overall, this study provides insights into antigenic variation and potential for cross-neutralizing epitopes on SARS-like viruses.

scholarly journals D Dimer – Prognostic indicator for disease severity in patients hospitalised with COVID 19

2021 ◽  
Vol 8 (4) ◽  
pp. 461-464
Author(s):  
Vineet Banga ◽  
Stuti Jain
Keyword(s):  
Retrospective Study ◽  
Disease Severity ◽  
Severe Disease ◽  
Prognostic Indicator ◽  
Clinical Severity ◽  
Care Hospital ◽  
Severity Of Disease ◽  
Management Protocol ◽  
Severity Levels ◽  
D Dimer

Patients of Covid 19 infections present with different severity. Levels of D Dimer in these patients can be correlated with disease severity for management and prognosis. To evaluate the usefulness of D-Dimer levels in blood to correlate with disease severity in COVID 19 patients. Retrospective study was done in Department of Pathology of Secondary Care hospital that became designated covid hospital from May 2021 to June 2021 on 60 COVID 19 positive admitted patients. D dimer levels were analysed and correlated with clinical severity of disease. Out of total 60 patients, 33 were in mild, 23 in moderate and 4 were in severe category. In mild cases D Dimer varies from 43 ng/ml to 183 ng/ml. In moderate cases D Dimer varies from 270 ng/ml to 991 ng/ml. In severe cases D Dimer varies from 1043 ng/ml to 2463 ng/ml. The study suggests cut off levels for D Dimer as up to 200 ng/ml for mild, 200-1000 ng/ml for moderate and more than 1000 ng/ml for severe category in COVID 19 patients. D dimer helps in identifying severe disease and can be used as an essential biomarker in developing the management protocol for COVID 19 patients.

scholarly journals Validation of Predictors of Disease Severity and Outcomes in COVID-19 Patients: A Descriptive and Retrospective Study

Med ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 128-138.e3 ◽  
Author(s):  
Li Tan ◽  
Xia Kang ◽  
Xinran Ji ◽  
Gaoming Li ◽  
Qi Wang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Disease Severity
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