Dataset Information

COVID-19 spike-host cell receptor GRP78 binding site prediction.

ABSTRACT:

Objectives

Understanding the novel coronavirus (COVID-19) mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition.

Methods

In this study, the COVID-19 spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The COVID-19 spike protein is modeled using its counterpart, the SARS spike.

Results

Sequence and structural alignments show that four regions, in addition to its cyclic nature have sequence and physicochemical similarities to the cyclic Pep42. Protein-protein docking was performed to test the four regions of the spike that fit tightly in the GRP78 Substrate Binding Domain ? (SBD?). The docking pose revealed the involvement of the SBD? of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor.

Conclusions

We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8?kcal/mol. These nine residues can be used to develop therapeutics specific against COVID-19.

SUBMITTER: Ibrahim IM

PROVIDER: S-EPMC7102553 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

COVID-19 spike-host cell receptor GRP78 binding site prediction.

Ibrahim Ibrahim M IM Abdelmalek Doaa H DH Elshahat Mohammed E ME Elfiky Abdo A AA

The Journal of infection 20200310 5

<h4>Objectives</h4>Understanding the novel coronavirus (COVID-19) mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition.<h4>Methods</h4>In this study, the COVID-19 spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The COVID-19 spike protein is modeled using its counte ...[more]

PMID: 32169481

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Project description:BACKGROUNDSerological assays are of critical importance to investigate correlates of response and protection in coronavirus disease 2019 (COVID-19), to define previous exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations, and to verify the development of an adaptive immune response in infected individuals.METHODSWe studied 509 patients confirmed to have COVID-19 from the San Raffaele Hospital of Milan and 480 samples of prepandemic organ donor sera collected in 2010-2012. Using fluid-phase luciferase immune precipitation (LIPS) assays, we characterized IgG, IgM, and IgA antibodies to the spike receptor binding domain (RBD), S1+S2, nucleocapsid, and ORF6 to ORF10 of SARS-CoV-2, to the HCoV-OC43 and HCoV-HKU1 betacoronaviruses spike S2, and the H1N1Ca2009 flu virus hemagglutinin. Sequential samples at 1 and 3 months after hospital discharge were also tested for SARS-CoV-2 RBD antibodies in 95 patients.RESULTSAntibodies developed rapidly against multiple SARS-CoV-2 antigens in 95% of patients by 4 weeks after symptom onset and IgG to the RBD increased until the third month of follow-up. We observed a major synchronous expansion of antibodies to the HCoV-OC43 and HCoV-HKU1 spike S2. A likely coinfection with influenza was neither linked to a more severe presentation of the disease nor to a worse outcome. Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike RBD was predictive of survival.CONCLUSIONThe measurement of antibodies to selected epitopes of SARS-CoV-2 antigens can offer a more accurate assessment of the humoral response in patients and its impact on survival. The presence of partially cross-reactive antibodies with other betacoronaviruses is likely to impact on serological assay specificity and interpretation.TRIAL REGISTRATIONCOVID-19 Patients Characterization, Biobank, Treatment Response and Outcome Predictor (COVID-BioB). ClinicalTrials.gov identifier: NCT04318366.FUNDINGIRCCS Ospedale San Raffaele and Università Vita Salute San Raffaele.

Dataset Information

COVID-19 spike-host cell receptor GRP78 binding site prediction.

Objectives

Methods

Results

Conclusions

Publications

COVID-19 spike-host cell receptor GRP78 binding site prediction.

Similar Datasets

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