ArticleThe Journal of biological chemistry
The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2 and GRP78 depleting antibody blocks viral entry and infection.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Unveiling the dark side of glucose-regulated protein 78 (GRP78) in cancers and other human pathology: a systematic review.Molecular medicine (Cambridge, Mass.) · 2023Pooled it
- GRP78 dysregulation: A proposed molecular mechanism linking the tumor microenvironment to sepsis susceptibility in patients with cancer (Review).International journal of molecular medicine · 2026Review
- GRP78 in viral pneumonia: dual regulatory mechanisms and translational prospects.Clinical and experimental medicine · 2026Review
- Glutamine-Linked Cellular Stress Responses in Viral Infection: Mechanisms, Crosstalk, and Future Perspectives.International journal of molecular sciences · 2026Review
- GRP78 promotes rabies virus entry through interacting with viral receptors.Journal of virology · 2026Article
- Nisin and rutin as potential coating agents for iron oxide nanoparticles for enhanced theranostic applications against cancer.Scientific reports · 2026Article
- Review
- Molecular Characterization of Calu-3 Cells from Submerged to Air-Liquid Interface to Model Lung Infections.Journal of proteome research · 2026Article
- Identification of Cathepsin L as the Molecular Target of Hydroxychloroquine With Chemical Proteomics.Molecular & cellular proteomics : MCP · 2025Article
- Expression of SARS-CoV-2 entry-associated proteins in COPD airways: an immunohistochemical study.The Journal of pathology · 2025Article
- HSPA5, a Host Cellular Heat-Shock Protein Required for Influenza a Virus Replication.International journal of molecular sciences · 2025Article
- From zoonotic spillover to endemicity: the broad determinants of human coronavirus tropism.mBio · 2025Review
- The Clinical Significance of GRP78 in COVID-19 Pneumonia Across Two Regional Cohorts.International journal of molecular sciences · 2025Article
- Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- Screening of Medicinal Herbs IdentifiesViruses · 2025Article
- Stress-induced translocation of the endoplasmic reticulum chaperone GRP78/BiP and its impact on human disease and therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Receptor Binding for the Entry Mechanisms of SARS-CoV-2: Insights from the Original Strain and Emerging Variants.Viruses · 2025Review
- Exploring the therapeutic potential of Thymus vulgaris ethanol extract: a computational screening for antimicrobial compounds against COVID-19 induced mucormycosis.Scientific reports · 2025Article
- A humanized antibody against mucormycosis targets angioinvasion and augments the host immune response.Science translational medicine · 2025Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 global pandemic, utilizes the host receptor angiotensin-converting enzyme 2 (ACE2) for viral entry. However, other host factors might also play important roles in SARS-CoV-2 infection, providing new directions for antiviral treatments. GRP78 is a stress-inducible chaperone important for entry and infectivity for many viruses. Recent molecular docking analyses revealed putative interaction between GRP78 and the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (SARS-2-S). Here we report that GRP78 can form a complex with SARS-2-S and ACE2 on the surface and at the perinuclear region typical of the endoplasmic reticulum in VeroE6-ACE2 cells and that the substrate-binding domain of GRP78 is critical for this interaction. In vitro binding studies further confirmed that GRP78 can directly bind to the RBD of SARS-2-S and ACE2. To investigate the role of GRP78 in this complex, we knocked down GRP78 in VeroE6-ACE2 cells. Loss of GRP78 markedly reduced cell surface ACE2 expression and led to activation of markers of the unfolded protein response. Treatment of lung epithelial cells with a humanized monoclonal antibody (hMAb159) selected for its safe clinical profile in preclinical models depleted cell surface GRP78 and reduced cell surface ACE2 expression, as well as SARS-2-S-driven viral entry and SARS-CoV-2 infection in vitro. Our data suggest that GRP78 is an important host auxiliary factor for SARS-CoV-2 entry and infection and a potential target to combat this novel pathogen and other viruses that utilize GRP78 in combination therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.