MDL-001: An Oral, Safe, and Well-Tolerated Broad-Spectrum Inhibitor of Viral Polymerases

The death toll and financial stress posed by the recent COVID-19 pandemic have highlighted the pressing need to develop safe and effective, broad-spectrum inhibitors to treat viral infections. To accelerate the antiviral drug discovery process, we developed GALILEO™, a computational platform that interfaces with a customizable bioinformatics pipeline with a geometric deep learning algorithm we named ChemPrint™ for in silico drug screening. Combining these algorithms with a large chemical repositioning library, we discovered MDL-001, which interacts with the Thumb pocket 1 subdomain of multiple single-stranded RNA viruses. For MDL-001, we demonstrate potent in vitro activity against a broad spectrum of pathogenic viruses, and we demonstrate potent in vivo efficacy in a mouse model of SARS-CoV-2 infection. In clinical trials, orally administered MDL-001 has been shown to be safe and well tolerated. These data underline both the effectiveness of the GALILEO™ platform for drug discovery and the promise of MDL-001 as a novel broad-spectrum antiviral clinical candidate.