Ephrin (Eph) receptor and downstream signaling pathways: a promising potential targeted therapy for COVID‑19 and associated cancers and diseases
Ce dossier présente un ensemble d'articles concernant la prise en charge des cancers durant la crise sanitaire liée au COVID-19
Dear Editor, Currently, the coronavirus disease 2019 (COVID-19) pandemic has become a serious concern to the worldwide healthcare system. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 and the emergence of new SARS-CoV-2 variants such as Omicron with higher potency for spread and infectivity, as well as immune scape characteristics toward vaccines can encourage us to provide new therapeutic insights for this disease. Recently, in a study, we described Ephrin (Eph) receptors as a possible SARS-CoV-2 entry receptor for human host cells in the central nervous system (CNS) and the potential roles of SARS-CoV-2 spike protein in stimulating the Eph receptor downstream signaling pathway for COVID-19-associated neurodegenerative diseases [1]. In addition, studies have shown that Eph receptors express in a variety of tissues and organs such as the lung, liver, colon, small intestine, prostate, kidney, heart, etc. [2]. Thus, their cells could be potential host cells for SARS-CoV-2 to enter and/or stimulate downstream signaling pathways.
The SARS-CoV-2 receptor-binding motif (RBM) was discovered in another study by Beaudoin. Ch et al. to mimic ephrin-A5 and ephrin-B2 that bind to the ephrin type 4a receptor (EphA4). Accordingly, docking data indicated similar affinity values between the SARS-CoV-2 RBM–EphA4, ephrin-A5–EphA4, and experimental (PDB: 4m4r) complexes of -1.41, -3.32, and -0.45 kJ/mol, respectively.
In addition, researchers discovered that EphA2 promotes the intracellular fusion and internalization of Epstein–Barr Virus (EBV) by interacting with its encoded proteins gH/gL and gB, and the Ephrin ligand-binding domain and Ephrin fibronectin domain are necessary for EphA2-mediated EBV infection. Based on these results, EphA2 is necessary for EBV entry into epithelial cells. Furthermore, EphA2 may act as a co-receptors for hepatitis C virus (HCV) entry and tyrosine kinase inhibitors appear to have significant antiviral properties. The Eph receptor pathway is nearly entirely responsible for Ross River virus (RRV) entry into B cells and endothelial cells, whereas the Eph receptor is not necessary for RRV entry into fibroblasts and epithelial cells [4].
Here, we discussed other possible signaling pathways of Eph receptors that could be stimulated by SARS-CoV-2 spike protein in other diseases (especially cancer progression) as potential promising targeted therapy (...)
Human Cell , éditorial en libre accès, 2022