Garcinone C inhibits pseudorabies virus replication through EGF/PI3K/Akt axis

Area of Science:

• Virology
• Pharmacology
• Immunology

Background:

• Pseudorabies virus (PRV) poses significant economic and public health risks due to its zoonotic potential.
• Evolving PRV strains challenge the efficacy of existing vaccines and antiviral treatments.
• Novel therapeutic strategies are urgently needed to control PRV spread.

Purpose of the Study:

• To evaluate the antiviral activity of garcinone C against PRV replication.
• To elucidate the molecular mechanisms underlying garcinone C's inhibitory effects.
• To assess the therapeutic potential of garcinone C in vivo.

Main Methods:

• In vitro and in vivo assays to assess PRV replication inhibition by garcinone C.
• Time-of-addition experiments to determine the stage of antiviral action.
• RNA sequencing and KEGG pathway analysis to identify differentially expressed genes and affected pathways.
• Cytokine level measurements (IL-6, IL-8, TNF-α).
• Animal studies involving oral administration of garcinone C to PRV-infected mice.

Main Results:

• Garcinone C inhibited PRV replication in a dose- and time-dependent manner, specifically when administered post-infection.
• Transcriptomic analysis revealed that garcinone C's antiviral effect is linked to the PI3K-Akt signaling pathway, potentially via downregulation of epidermal growth factor.
• Garcinone C suppressed the production of inflammatory cytokines (IL-6, IL-8, TNF-α) and improved survival rates, reduced pathology, and viral loads in infected mice.

Conclusions:

• Garcinone C demonstrates significant therapeutic potential as an antiviral agent against PRV.
• The PI3K-Akt signaling pathway is a key target for garcinone C's mechanism of action against PRV.
• Garcinone C represents a promising candidate for developing new treatments to combat PRV infections.