Article ; Online: Glyceraldehyde-3-Phosphate Dehydrogenase Binds with Spike Protein and Inhibits the Entry of SARS-CoV-2 into Host Cells.
2024 Volume 16, Issue 1, Page(s) 133–142
Abstract: Introduction: Coronavirus disease 2019 caused by coronavirus-2 (SARS-CoV-2) has emerged as an aggressive viral pandemic. Health care providers confront a challenging task for rapid development of effective strategies to combat this and its long-term ... ...
| Abstract | Introduction: Coronavirus disease 2019 caused by coronavirus-2 (SARS-CoV-2) has emerged as an aggressive viral pandemic. Health care providers confront a challenging task for rapid development of effective strategies to combat this and its long-term after effects. Virus entry into host cells involves interaction between receptor-binding domain (RBD) of spike (S) protein S1 subunit with angiotensin converting enzyme present on host cells. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a moonlighting enzyme involved in cellular glycolytic energy metabolism and micronutrient homeostasis. It is deployed in various cellular compartments and the extra cellular milieu. Though it is known to moonlight as a component of mammalian innate immune defense machinery, till date its role in viral restriction remains unknown. Method: Recombinant S protein, the RBD, and human GAPDH protein were used for solid phase binding assays and biolayer interferometry. Pseudovirus particles expressing four different strain variants of S protein all harboring ZsGreen gene as marker of infection were used for flow cytometry-based infectivity assays. Results: Pseudovirus entry into target cells in culture was significantly inhibited by addition of human GAPDH into the extracellular medium. Binding assays demonstrated that human GAPDH binds to S protein and RBD of SARS-CoV-2 with nanomolar affinity. Conclusions: Our investigations suggest that this interaction of GAPDH interferes in the viral docking with hACE2 receptors, thereby affecting viral ingress into mammalian cells. |
|---|---|
| MeSH term(s) | Humans ; Spike Glycoprotein, Coronavirus/metabolism ; SARS-CoV-2/physiology ; COVID-19/virology ; Protein Binding ; Virus Internalization ; HEK293 Cells ; Betacoronavirus/physiology ; Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism ; Pneumonia, Viral/virology ; Pneumonia, Viral/immunology ; Pandemics ; Coronavirus Infections/virology ; Angiotensin-Converting Enzyme 2/metabolism ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) |
| Chemical Substances | Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Glyceraldehyde-3-Phosphate Dehydrogenases (EC 1.2.1.-) ; GAPDH protein, human (EC 1.2.1.12) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; ACE2 protein, human (EC 3.4.17.23) ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) (EC 1.2.1.12) |
| Language | English |
| Publishing date | 2024-02-07 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; News |
| ZDB-ID | 2454158-8 |
| ISSN | 1662-8128 ; 1662-811X |
| ISSN (online) | 1662-8128 |
| ISSN | 1662-811X |
| DOI | 10.1159/000535634 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 6727: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.