Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) binds with spike protein and inhibits the entry of SARS-CoV-2 into host cells.

Publication date: Feb 07, 2024

Coronavirus disease 2019 (COVID-19) 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 (ACE) 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. Recombinant S protein, the receptor binding domain (RBD) and human GAPDH protein were used for solid phase binding assays and Biolayer interferometry (BLI). Pseudo virus 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. Pseudo-virus 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 domain of SARS-CoV-2 with nano molar affinity. Our investigations suggest that this interaction of GAPDH interferes in the viral docking with hACE2 receptors, thereby affecting viral ingress into mammalian cells.

Concepts Keywords
Aggressive Assays
Coronavirus Binding
Glyceraldehyde Cells
Homeostasis Cellular
Moonlight Cov


Type Source Name
drug DRUGBANK Glyceraldehyde-3-Phosphate
disease IDO host
disease MESH Coronavirus disease 2019
disease VO effective
disease IDO entry into host
drug DRUGBANK Angiotensin II
disease VO gene
disease MESH infection
disease IDO infectivity

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