Matrine activates high xenophagy to inhibit enterovirus replication

Area of Science:

• Virology
• Cell Biology
• Pharmacology

Background:

• Enteroviruses cause significant morbidity and mortality, necessitating novel antiviral treatments.
• Existing vaccines and drugs for enteroviruses are limited, highlighting the need for new therapeutic agents.

Purpose of the Study:

• To investigate the antiviral potential of matrine against Enterovirus D68 (EVD68) and Coxsackievirus A6 (CVA6).
• To elucidate the mechanism of matrine's antiviral activity, building on prior research against Enterovirus A71 (EVA71).

Main Methods:

• Utilized techniques including western blotting, RT-PCR, and cell-based assays to assess viral replication and protein expression.
• Employed gene knockdown/knockout and co-immunoprecipitation to analyze molecular interactions and mechanisms.

Main Results:

• Matrine demonstrated broad-spectrum antiviral activity against EVA71, EVD68, and CVA6 by inhibiting viral replication.
• Matrine activates autophagy, upregulating LC3 expression, and directly reduces viral protein VP3 levels.
• VP3 binding to P62 was identified as crucial for VP3 degradation and matrine's antiviral efficacy.

Conclusions:

• Matrine activates autophagy to promote viral protein VP3 degradation, thereby inhibiting enterovirus replication.
• Matrine represents a promising candidate for developing novel, broad-spectrum anti-enterovirus therapeutics.