Heat shock protein 70 (Hsp70) is involved in the Zika virus cellular infection process

Pujhari, Sujit; Vm, Macias; Rh, Nissly; Nomura, Masashi; Kuchipudi, Suresh V.; Jl, Rasgon

doi:10.1101/135350

Cited by 8 publications

(9 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The predicted binding site of the Spike protein to GRP7 found in this study is in good agreement with studies that identified the spike receptor-binding domain using antibodies 23,41 .…”

Section: Binding Mode Of Spike-grp78supporting

confidence: 89%

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

Ibrahim

Abdelmalek

El-Shahat

et al. 2020

Journal of Infection

434

382

View full text Add to dashboard Cite

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.

show abstract

“…The predicted binding site of the Spike protein to GRP7 found in this study is in good agreement with studies that identified the spike receptor-binding domain using antibodies 23,41 .…”

Section: Binding Mode Of Spike-grp78supporting

confidence: 89%

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

Ibrahim

Abdelmalek

El-Shahat

et al. 2020

Journal of Infection

434

382

View full text Add to dashboard Cite

show abstract

“…The predicted binding site of the Spike protein to GRP7 found in this study is in good agreement with studies that identified the spike receptor-binding domain using antibodies 23,41 . Knowledge of this…”

Section: Binding Mode Of Spike-grp78supporting

confidence: 89%

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

Ibrahim

Abdelmalek

Elshahat

et al. 2020

Preprint

152

192

View full text Add to dashboard Cite

Coronaviruses have been circulating between animals and humans repeatedly. A novel human coronavirus, named COVID-19, has recently emerged in Hubei Province, China.Within the first two months, more than 2200 deaths have been confirmed, and there have been more than 79,000 hospitalized patients, mainly in China. Understanding the virus 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. In this study, the COVID-19 corona viral spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The cyclic peptide Pep42 (CTVALPGGYVRVC) was reported earlier to be the docking platform of GRP78 in cancer cells. The COVID-19 spike protein is modeled using its counterpart, the SARS spike. Sequence and structural alignments show that four regions, in addition to its cyclic nature (the S-S bond), 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. 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 (region IV) of the spike can be used to develop therapeutics specific against COVID-19.

show abstract

“…It is now established that ZIKV tropism is mediated by cell surface receptors DC-SIGN, AXL, heat shock proteins, TYRO3, and TIM-1. 55,56 AXL is a phosphatidylserine protein that belongs to the TAM receptor family of phagocytic receptors 57 and it appears to play an important role in ZIKV infection of a wide range of cells of organ systems targeted by this virus, as discussed below. However, ZIKV may also use a combination of different cell surface/adhesion molecules to gain cellular entry.…”

Section: Cellular Mechanisms Of Zikv Tropism: Receptor-mediated and Rmentioning

confidence: 99%

Insights into the molecular roles of Zika virus in human reproductive complications and congenital neuropathologies

Gharbaran

Somenarain

2017

Pathology

View full text Add to dashboard Cite

The recent upsurge in the association of congenital neurological disorders and infection by the Zika virus (ZIKV) has resulted in increased research focus on the biology of this flavivirus. Studies in animal models indicate that ZIKV can breach the placental barrier and selectively infect and deplete neuroprogenitor cells (NPCs) of the developing fetus, resulting in changes of brain structures, reminiscent of human microcephaly. In vitro and ex vivo studies using human cells and tissues showed that human NPCs and placental cells are targeted by ZIKV. Also of concern is the impact of ZIKV on human reproductive structures, with the potential to cause infertility, as the virus appears to remain in the genital tract for extended periods of time. This review discusses the putative roles of ZIKV on human reproductive complications and congenital neuropathologies.

show abstract

Heat shock protein 70 (Hsp70) is involved in the Zika virus cellular infection process

Cited by 8 publications

References 41 publications

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

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

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

Insights into the molecular roles of Zika virus in human reproductive complications and congenital neuropathologies

Contact Info

Product

Resources

About