Model Medicines Reveals Breakthrough AI Discovery: RdRp Thumb-1, A Universal RNA Antiviral Target, and MDL-001, a Potent Inhibitor

Model Medicines is excited to share our latest breakthrough in antiviral drug discovery with the publication of our new preprint, "Discovery of RdRp Thumb-1 as a novel broad-spectrum antiviral family of targets and MDL-001 as a potent broad-spectrum inhibitor thereof - Part I: A Bioinformatics and Deep Learning Approach," now accessible on bioRxiv. This publication highlights our commitment to leveraging advanced AI to push the boundaries of drug discovery, particularly in uncovering novel biology and chemistry for the development of broad-spectrum antivirals.

Highlights

• Innovative Target Discovery: Identified the highly conserved Thumb-1 site of the viral RNA-dependent RNA polymerase (RdRp) as a promising new target for broad-spectrum antivirals across many pathogenic RNA viruses through our state-of-the-art AI platform, GALILEO™.

• MDL001, A Potent Broad-Spectrum Inhibitor: Discovered MDL-001, a potent inhibitor of the RdRp Thumb-1 site across multiple virus families, using our proprietary GALILEO™ AI platform and ChemPrint model. MDL-001 showcases the potential for a universal antiviral treatment.

• SARS-CoV-2: Showed MDL-001's nanomolar efficacy against SARS-CoV-2 variants in cell-based assays, reduction of viral load in a mouse model of SARS-CoV-2 infection, and potential best-in-class lung penetration compared to approved oral antivirals like Paxlovid.

• Cutting-Edge AI Techniques: The discovery process utilized advanced bioinformatics and deep learning approaches, underscoring Model Medicines' forefront position in AI-driven drug discovery. We demonstrated the superiority of our AI models in identifying MDL-001 as a potential Thumb-1 inhibitor, compared to conventional virtual screening methods like molecular docking.

• Pandemic Preparedness: The discovery of the conserved RdRp Thumb-1 site as a druggable target across pathogenic RNA viruses, and MDL-001 as a potent and orally bioavailable inhibitor, represent major breakthroughs in our efforts to develop broad-spectrum antivirals. This work has the potential to transform our ability to combat viral outbreaks and enhance global pandemic preparedness.

• Strategic Antiviral Development: This research paves the way for developing novel antiviral therapies, addressing the urgent need for effective treatments against multiple viral pathogens. By leveraging our advanced machine-learning techniques, we can uncover novel druggable targets and identify potent inhibitors that may be missed by traditional approaches. Our AI-driven strategy enables us to respond to current and future viral threats rapidly.

• Strengthening National Security: The development of broad-spectrum antivirals like MDL-001 is crucial for safeguarding national security. By rapidly responding to emerging viral threats, we can minimize the devastating health, economic, and social impacts of pandemics. Our AI-driven approach to antiviral discovery empowers governments and public health organizations to proactively address viral outbreaks, ensuring the safety and stability of our nation.

We invite the scientific community, potential collaborators, and the public to explore our preprint's detailed findings and innovative methodologies.