Ribavirin

Ribavirin is a synthetic guanosine analog with broad-spectrum antiviral activity. It is metabolized intracellularly to its active triphosphate form, which inhibits viral RNA-dependent RNA polymerase and induces lethal mutagenesis in viral genomes. Ribavirin also inhibits inosine monophosphate dehydrogenase (IMPDH), reducing GTP synthesis and viral replication. It has demonstrated EC₅₀ values ranging from 2-95 µg/mL across various RNA and DNA viruses and 109.5 µM against SARS-CoV-2 in Vero cells.

Key features and applications include:

• Broad Antiviral Spectrum: Active against both RNA and DNA viruses, including RSV, HCV, HIV, influenza, and coronaviruses.
• Multiple Mechanisms of Action: Inhibits viral polymerases, depletes GTP pools via IMPDH inhibition, and induces error catastrophe in viral genomes.
• Versatile Administration: Used in oral, intravenous, and aerosolized forms in clinical and research settings.
• Combination Therapy: Commonly used with interferon-α or direct-acting antivirals (DAAs) in hepatitis C treatment.

Research Applications:

• Antiviral drug screening
• Viral replication and mutagenesis studies
• Host-virus interaction models
• Immunomodulatory and anti-inflammatory research

Relevant disease states include:

• Hepatitis C Virus (HCV): Historically used in combination therapy to enhance viral clearance.
• Respiratory Syncytial Virus (RSV): Administered via aerosol in severe pediatric infections.
• Viral Hemorrhagic Fevers: Investigated for use in Lassa fever and other high-mortality viral infections.
• COVID-19: Studied for its potential to inhibit SARS-CoV-2 replication.
• Cancer Research: Shown to inhibit tumor growth and metastasis in soft tissue sarcomas by downregulating PRMT1 and PRMT5.