Rapid Screening to Identify Antivirals against Persistent and Acute Coxsackievirus B3 Infection

Area of Science:

• Virology
• Antiviral Drug Discovery
• Molecular Biology

Background:

• Enteroviruses, including Coxsackievirus B3 (CVB3), cause significant global health issues.
• Persistent CVB3 infection, where the virus is not cleared, poses a therapeutic challenge.
• Current antiviral options for CVB3 are limited, necessitating new drug development.

Purpose of the Study:

• To identify novel antiviral compounds effective against both acute and persistent CVB3 infections.
• To establish a model system for studying persistent CVB3 infection.
• To evaluate the antiviral potential of identified compounds in relevant cell lines.

Main Methods:

• Developed a PANC-1 cell model for persistent CVB3 infection and used Vero-E6 cells for acute infection.
• Screened thousands of compounds via the NIH's Developmental Therapeutics Program (DTP).
• Assessed antiviral activity, cytotoxicity, and mechanism of action of hit compounds.

Main Results:

• Identified Ro 5-3335, a benzodiazepine, as a potent inhibitor of CVB3 in both acute and persistent infections.
• Ro 5-3335 demonstrated antiviral activity across multiple cell types with minimal cytotoxicity.
• Viral egress was identified as a potential target for Ro 5-3335's antiviral action.

Conclusions:

• Ro 5-3335 is a promising candidate for treating CVB3 infections, including persistent forms.
• The compound shows broad-spectrum activity against RNA viruses but not DNA viruses.
• Further research into Ro 5-3335 could lead to new therapies for enterovirus infections.