ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection

Engler, Melanie; Albers, Dan; Maltitz, Pascal von; Groß, Rüdiger; Münch, Jan; Cirstea, Ion Cristian

doi:10.26508/lsa.202201880

Cited by 8 publications

(9 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18 In addition, advanced docking analysis between EGFR and SARS-CoV-2 S protein in glioma cells showed a similar binding affinity to that between ACE2 and S protein. 52,59 These findings highlight a significant correlation between EGFR activation and regulation of SARS-CoV-2 infection.…”

Section: Activation Of Epidermal Growth Factor Receptor Signalling In...mentioning

confidence: 77%

“…20 Meanwhile, S protein of SARS-CoV-2 activates MAPK through the ACE2-EGFR axis, which may facilitate the SARS-CoV-2 infection. 52 These studies suggest that the S protein of SARS-CoV-2 interacts with EGFR and this interaction may be involved in SARS-CoV-2 replication. The EGFR gene expression is also promoted at transcriptional levels upon SARS-CoV-2 infection, as it elevates mitochondrial bioenergetics and promotes the process of oxidative phosphorylation (OXPHOS) to induce robust virus propagation.…”

Section: Activation Of Epidermal Growth Factor Receptor Signalling In...mentioning

confidence: 88%

See 1 more Smart Citation

Targeting epidermal growth factor receptor signalling pathway: A promising therapeutic option for COVID‐19

Razzaq,

Disoma,

Zhou

et al. 2023

Reviews in Medical Virology

View full text Add to dashboard Cite

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long‐term health issues linked to long COVID‐19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS‐CoV‐2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response. Over the long term, EGFR activation in COVID‐19, particularly in COVID‐19‐induced pulmonary fibrosis, may be linked to the development of lung cancer. In this review, we have summarised the significance of EGFR signalling in the context of SARS‐CoV‐2 infection. We also discussed the targeting of EGFR signalling as a promising strategy for COVID‐19 treatment and highlighted erlotinib as a superior option among EGFR inhibitors. Erlotinib effectively blocks EGFR and AAK1, thereby preventing SARS‐CoV‐2 replication, reducing mucus hyperproduction, TNF‐α expression, and enhancing the host's antiviral response. Nevertheless, to evaluate the antiviral efficacy of erlotinib, relevant clinical trials involving an appropriate patient population should be designed.

show abstract

Section: Activation Of Epidermal Growth Factor Receptor Signalling In...mentioning

confidence: 77%

Section: Activation Of Epidermal Growth Factor Receptor Signalling In...mentioning

confidence: 88%

Targeting epidermal growth factor receptor signalling pathway: A promising therapeutic option for COVID‐19

Razzaq,

Disoma,

Zhou

et al. 2023

Reviews in Medical Virology

View full text Add to dashboard Cite

show abstract

“…4 ). Considering the top ten enriched pathways, the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt) signaling and the EGFR tyrosine kinase inhibitor resistance, two pathways associated to SARS-CoV-2 infection 31 , 32 , were predominantly enriched in both Severe and Moderate cases. In contrast, miRNA targets enriched in the age-associated receptor for advanced glycation endproducts (AGE-RAGE) signaling, a pathway associated to COVID-19 severity 33 , were only observed in patients requiring intensive care (severe cases).…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 remodels the landscape of small non-coding RNAs with infection time and symptom severity

Corell-Sierra,

Marquez-Molins,

Marqués

et al. 2024

npj Syst Biol Appl

View full text Add to dashboard Cite

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has significantly impacted global health, stressing the necessity of basic understanding of the host response to this viral infection. In this study, we investigated how SARS-CoV-2 remodels the landscape of small non-coding RNAs (sncRNA) from a large collection of nasopharyngeal swab samples taken at various time points from patients with distinct symptom severity. High-throughput RNA sequencing analysis revealed a global alteration of the sncRNA landscape, with abundance peaks related to species of 21-23 and 32-33 nucleotides. Host-derived sncRNAs, including microRNAs (miRNAs), transfer RNA-derived small RNAs (tsRNAs), and small nucleolar RNA-derived small RNAs (sdRNAs) exhibited significant differential expression in infected patients compared to controls. Importantly, miRNA expression was predominantly down-regulated in response to SARS-CoV-2 infection, especially in patients with severe symptoms. Furthermore, we identified specific tsRNAs derived from Glu- and Gly-tRNAs as major altered elements upon infection, with 5’ tRNA halves being the most abundant species and suggesting their potential as biomarkers for viral presence and disease severity prediction. Additionally, down-regulation of C/D-box sdRNAs and altered expression of tinyRNAs (tyRNAs) were observed in infected patients. These findings provide valuable insights into the host sncRNA response to SARS-CoV-2 infection and may contribute to the development of further diagnostic and therapeutic strategies in the clinic.

show abstract

“…Pre-infection positive regulation of MAPK-ERK1/2 pathways showed a positive correlation with AT2s’ susceptibility to SARS-CoV-2 infection and postinfection viral load. A recent study showed that treatment of Caco-2 cells with SARS-CoV-2 spike protein’s receptor binding domain activated the key mediators (ERK1/2 and CRAF) of MAPK signaling, and inhibition of MAPK signaling by MEK inhibitors reduced SARS-CoV-2 infection [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Pre-Infection Innate Immunity Attenuates SARS-CoV-2 Infection and Viral Load in iPSC-Derived Alveolar Epithelial Type 2 Cells

Kumar,

Granados,

Aceves

et al. 2024

Cells

View full text Add to dashboard Cite

A large portion of the heterogeneity in coronavirus disease 2019 (COVID-19) susceptibility and severity of illness (SOI) remains poorly understood. Recent evidence suggests that SARS-CoV-2 infection-associated damage to alveolar epithelial type 2 cells (AT2s) in the distal lung may directly contribute to disease severity and poor prognosis in COVID-19 patients. Our in vitro modeling of SARS-CoV-2 infection in induced pluripotent stem cell (iPSC)-derived AT2s from 10 different individuals showed interindividual variability in infection susceptibility and the postinfection cellular viral load. To understand the underlying mechanism of the AT2′s capacity to regulate SARS-CoV-2 infection and cellular viral load, a genome-wide differential gene expression analysis between the mock and SARS-CoV-2 infection-challenged AT2s was performed. The 1393 genes, which were significantly (one-way ANOVA FDR-corrected p ≤ 0.05; FC abs ≥ 2.0) differentially expressed (DE), suggest significant upregulation of viral infection-related cellular innate immune response pathways (p-value ≤ 0.05; activation z-score ≥ 3.5), and significant downregulation of the cholesterol- and xenobiotic-related metabolic pathways (p-value ≤ 0.05; activation z-score ≤ −3.5). Whilst the effect of post-SARS-CoV-2 infection response on the infection susceptibility and postinfection viral load in AT2s is not clear, interestingly, pre-infection (mock-challenged) expression of 238 DE genes showed a high correlation with the postinfection SARS-CoV-2 viral load (FDR-corrected p-value ≤ 0.05 and r2-absolute ≥ 0.57). The 85 genes whose expression was negatively correlated with the viral load showed significant enrichment in viral recognition and cytokine-mediated innate immune GO biological processes (p-value range: 4.65 × 10−10 to 2.24 × 10−6). The 153 genes whose expression was positively correlated with the viral load showed significant enrichment in cholesterol homeostasis, extracellular matrix, and MAPK/ERK pathway-related GO biological processes (p-value range: 5.06 × 10−5 to 6.53 × 10−4). Overall, our results strongly suggest that AT2s’ pre-infection innate immunity and metabolic state affect their susceptibility to SARS-CoV-2 infection and viral load.

show abstract

ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infection

Cited by 8 publications

References 72 publications

Targeting epidermal growth factor receptor signalling pathway: A promising therapeutic option for COVID‐19

Targeting epidermal growth factor receptor signalling pathway: A promising therapeutic option for COVID‐19

SARS-CoV-2 remodels the landscape of small non-coding RNAs with infection time and symptom severity

Pre-Infection Innate Immunity Attenuates SARS-CoV-2 Infection and Viral Load in iPSC-Derived Alveolar Epithelial Type 2 Cells

Contact Info

Product

Resources

About