Andrographolide Prevents EV-D68 Replication by Inhibiting the Acidification of Virus-Containing Endocytic Vesicles

Area of Science:

• Virology
• Pharmacology
• Drug Discovery

Background:

• Enterovirus D68 (EV-D68) is a significant respiratory pathogen causing severe disease.
• Current therapeutic options, including antiviral agents and vaccines for EV-D68, are lacking.

Purpose of the Study:

• To investigate the antiviral activity of andrographolide (ADO), a component of *Andrographis paniculata*, against EV-D68.
• To elucidate the mechanism of action of ADO in inhibiting EV-D68 replication.

Main Methods:

• Assessed ADO's effect on EV-D68 RNA replication and protein synthesis.
• Evaluated ADO's impact on host immune activation, viral attachment, and endocytosis.
• Utilized a pH-sensitive fluorescent indicator for real-time endocytosis monitoring.

Main Results:

• ADO significantly inhibited EV-D68 RNA replication (EC50 = 3.45 μM) and protein synthesis.
• ADO demonstrated low cytotoxicity at effective concentrations.
• ADO was found to inhibit the acidification of endocytic vesicles, a critical step in EV-D68 entry and replication.

Conclusions:

• ADO exhibits potent antiviral activity against EV-D68 by disrupting the maturation of virus-containing endosomes.
• ADO represents a promising therapeutic candidate for developing novel antiviral treatments against EV-D68 infections.