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

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Summary

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 β (SBDβ). The docking pose revealed the involvement of the SBDβ 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.

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Most cited references 14

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Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein

Sandrine Belouzard, Jean K. Millet, Beth N. Licitra … (2012)

Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes—A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.

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PLIP: fully automated protein–ligand interaction profiler

Sebastian Salentin, Sven Schreiber, V. Haupt … (2015)

The characterization of interactions in protein–ligand complexes is essential for research in structural bioinformatics, drug discovery and biology. However, comprehensive tools are not freely available to the research community. Here, we present the protein–ligand interaction profiler (PLIP), a novel web service for fully automated detection and visualization of relevant non-covalent protein–ligand contacts in 3D structures, freely available at projects.biotec.tu-dresden.de/plip-web . The input is either a Protein Data Bank structure, a protein or ligand name, or a custom protein–ligand complex (e.g. from docking). In contrast to other tools, the rule-based PLIP algorithm does not require any structure preparation. It returns a list of detected interactions on single atom level, covering seven interaction types (hydrogen bonds, hydrophobic contacts, pi-stacking, pi-cation interactions, salt bridges, water bridges and halogen bonds). PLIP stands out by offering publication-ready images, PyMOL session files to generate custom images and parsable result files to facilitate successive data processing. The full python source code is available for download on the website. PLIP's command-line mode allows for high-throughput interaction profiling.

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Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease.

Jasper F W Chan, Susanna Lau, Kelvin K. W. To … (2015)

The source of the severe acute respiratory syndrome (SARS) epidemic was traced to wildlife market civets and ultimately to bats. Subsequent hunting for novel coronaviruses (CoVs) led to the discovery of two additional human and over 40 animal CoVs, including the prototype lineage C betacoronaviruses, Tylonycteris bat CoV HKU4 and Pipistrellus bat CoV HKU5; these are phylogenetically closely related to the Middle East respiratory syndrome (MERS) CoV, which has affected more than 1,000 patients with over 35% fatality since its emergence in 2012. All primary cases of MERS are epidemiologically linked to the Middle East. Some of these patients had contacted camels which shed virus and/or had positive serology. Most secondary cases are related to health care-associated clusters. The disease is especially severe in elderly men with comorbidities. Clinical severity may be related to MERS-CoV's ability to infect a broad range of cells with DPP4 expression, evade the host innate immune response, and induce cytokine dysregulation. Reverse transcription-PCR on respiratory and/or extrapulmonary specimens rapidly establishes diagnosis. Supportive treatment with extracorporeal membrane oxygenation and dialysis is often required in patients with organ failure. Antivirals with potent in vitro activities include neutralizing monoclonal antibodies, antiviral peptides, interferons, mycophenolic acid, and lopinavir. They should be evaluated in suitable animal models before clinical trials. Developing an effective camel MERS-CoV vaccine and implementing appropriate infection control measures may control the continuing epidemic.

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Author and article information

Contributors

Abdo A. Elfiky

Journal

Journal ID (nlm-ta): J Infect

Journal ID (iso-abbrev): J. Infect

Title: The Journal of Infection

Publisher: W.B. Saunders

ISSN (Print): 0163-4453

ISSN (Electronic): 1532-2742

Publication date PMC-release: 10 March 2020

Publication date (Electronic): 10 March 2020

Electronic Location Identifier:

Affiliations

[a ]Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt

[b ]College of Applied Medical Sciences, University of Al-Jouf, Saudi Arabia

Author notes

[* ]Corresponding author. abdo@ 123456sci.cu.edu.eg aelfiky@ 123456ictp.it

Article

Publisher ID: S0163-4453(20)30107-9

DOI: 10.1016/j.jinf.2020.02.026

PMC ID: 7102553

PubMed ID: 32169481

SO-VID: 0a047de7-eb55-4475-af23-7a8fb3e9df5e

License:

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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

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Summary

Objectives

Methods

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Conclusions

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Novel Coronavirus Disease COVID-19

Most cited references 14

Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein

PLIP: fully automated protein–ligand interaction profiler

Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease.

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