MDL-001: An Oral, Direct-Acting Broad-Spectrum Antiviral for Influenza-like Illness (ILI) and Chronic Hepatitis In Vivo

Background/Objectives: Endemic viral respiratory illnesses caused by influenza, RSV, and coronaviruses impose a global disease burden of hundreds of millions of infections and hundreds of thousands of deaths annually. Chronic hepatitis B and C infections persist in 254 million and 58 million people worldwide, respectively. No approved therapy addresses these viruses simultaneously. MDL-001 is an oral, direct-acting, broad-spectrum antiviral targeting the Thumb-1 allosteric site of viral polymerases.

Methods

Here, we evaluated the antiviral activity of MDL-001 in vitro in influenza A/B, RSV, SARS-CoV-2, endemic human coronaviruses, and hepatitis B/C/D. We next evaluated MDL-001 antiviral activity in vivo in H1N1, SARS-CoV-2, HCV, and HBV. MDL-001’s in vivo efficacy was compared head-to-head versus standards of care including oseltamivir, remdesivir, sofosbuvir, and tenofovir alafenamide, or through the literature comparison with nirmatrelvir and molnupiravir. Lastly, we evaluated the pharmacokinetics, metabolism, tolerability, and safety profile of MDL-001.