4-Hydroxychalcone Inhibits Human Coronavirus HCoV-OC43 by Targeting EGFR/AKT/ERK1/2 Signaling Pathway

Area of Science:

• Virology
• Pharmacology
• Immunology

Background:

• Human coronaviruses pose a significant threat to global health.
• Effective antiviral therapies for coronaviruses are urgently needed.

Purpose of the Study:

• To investigate the antiviral activity of 4-hydroxychalcone (4HCH) against human coronavirus HCoV-OC43.
• To elucidate the mechanism of action of 4HCH against HCoV-OC43 infection.

Main Methods:

• In vitro assays to assess cytopathic effect inhibition, viral protein, and RNA levels.
• In vivo studies using HCoV-OC43-infected suckling mice to evaluate survival rates.
• Analysis of the epidermal growth factor receptor (EGFR) signaling pathway and pro-inflammatory cytokine production.

Main Results:

• 4HCH significantly inhibited HCoV-OC43 cytopathic effects, viral load, and increased survival in infected mice.
• 4HCH targets early viral infection stages by binding to EGFR, inhibiting the EGFR/AKT/ERK1/2 pathway, and suppressing viral replication.
• 4HCH reduced pro-inflammatory cytokine and chemokine production in infected cells and animal models.

Conclusions:

• 4HCH demonstrates potent in vitro and in vivo antiviral activity against HCoV-OC43.
• EGFR is identified as a promising host target for developing novel antiviral drugs.
• 4HCH is a potential therapeutic candidate for treating human coronavirus infections.