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

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic.
• Angiotensin-converting enzyme 2 (ACE2) is a known SARS-CoV-2 receptor.
• Other cell receptors, like epidermal growth factor receptor (EGFR), are investigated as potential SARS-CoV-2 binding partners.

Purpose of the Study:

• To investigate the activation of the EGFR-MAPK signaling pathway during SARS-CoV-2 infection.
• To identify the role of EGFR as a potential cofactor in SARS-CoV-2 entry and infection.

Main Methods:

• Demonstration of EGFR-MAPK axis activation by the SARS-CoV-2 spike protein.
• Identification of crosstalk between ACE2 and EGFR.
• Inhibition of EGFR-MAPK activation to assess its impact on viral infection.

Main Results:

• SARS-CoV-2 spike protein activates the EGFR-MAPK signaling pathway.
• A novel crosstalk between ACE2 and EGFR was identified, influencing ACE2 levels and EGFR activation/localization.
• Inhibition of EGFR-MAPK signaling significantly reduced infection by SARS-CoV-2.

Conclusions:

• EGFR acts as a cofactor for SARS-CoV-2 infection.
• EGFR-MAPK pathway activation is crucial for efficient SARS-CoV-2 infection.
• Targeting the EGFR-MAPK pathway could be a therapeutic strategy against SARS-CoV-2.