tetano
Editor, Senior Moderator
J Infect. 2020 Mar 10. pii: S0163-4453(20)30107-9. doi: 10.1016/j.jinf.2020.02.026. [Epub ahead of print]
COVID-19 Spike-host cell receptor GRP78 binding site prediction.
Ibrahim IM[SUP]1[/SUP], Abdelmalek DH[SUP]1[/SUP], Elshahat ME[SUP]1[/SUP], Elfiky AA[SUP]2[/SUP].
Author information
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 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.
Copyright ? 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
KEYWORDS:
BiP; COVID-19 spike; GRP78; Pep42; protein-protein docking; structural bioinformatics
PMID:32169481DOI:10.1016/j.jinf.2020.02.026
COVID-19 Spike-host cell receptor GRP78 binding site prediction.
Ibrahim IM[SUP]1[/SUP], Abdelmalek DH[SUP]1[/SUP], Elshahat ME[SUP]1[/SUP], Elfiky AA[SUP]2[/SUP].
Author information
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 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.
Copyright ? 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
KEYWORDS:
BiP; COVID-19 spike; GRP78; Pep42; protein-protein docking; structural bioinformatics
PMID:32169481DOI:10.1016/j.jinf.2020.02.026
