Many of the most devastating infectious diseases are caused by RNA viruses, and Model Medicines is working on one compound to kill them all. The AI drug discoverer’s oral small molecule was able to reduce SARS-CoV levels in the lungs of infected mice and also neutralized other RNA viruses like hepatitis C, norovirus and flu in cultured cells.
The results were posted as a preprint on bioRxiv on Jan. 14, and Model Medicines announced them in a Jan. 21 press release. Preprints are early views of papers that have not yet been peer reviewed by other scientists.
In addition to reducing COVID virus levels in infected mice, Model Medicines’ compound, MDL-001, also slowed weight loss in the mice at a level comparable to remdesivir, the active component of COVID medication Veklury, according to the preprint. Its ability to reduce virus levels in the rodents’ lungs also surpassed that of nirmatrelvir, the active ingredient in Paxlovid, the biotech said in the release.
Along with the preprint, Model Medicines also announced the launch of a new initiative that endeavors to aim its AI-based drug discovery platform at certain disease areas or indications that represent urgent healthcare challenges. Fittingly, the first of these programs is called ViroMME, a play on the word virome, which refers to the collection of viruses that live in an ecosystem together. ViroMME seeks to combat infectious diseases with a preclinical pipeline that includes MDL-001 and 12 other new compounds, the firm said.
MDL-001 targets a part of the RNA-dependent RNA polymerase enzyme that the viruses use to replicate their genetic material. Model Medicines previously used its in silico AI model to determine that a region of the enzyme, Thumb-1, is broadly conserved across certain RNA viruses and that MDL-001 binds to it.
MDL-001 wasn’t as successful at inhibiting norovirus, hepatitis C and influenza as it was the tested coronaviruses, which included the alpha, beta, delta and omicron variants, along with the original strain of the virus that originated in Wuhan, China, according to the preprint.
"MDL-001 represents a significant potential step forward in pandemic preparedness,” study author Davey Smith, M.D., an infectious disease specialist at the University of California, San Diego (UCSD), said in the release. “Its broad-spectrum efficacy and oral bioavailability position it as a key tool for rapid deployment during viral outbreaks.”
MDL-001's chemical name is pipendoxifene, and it was originally tested for breast cancer by Ligand Pharmaceuticals and Wyeth-Ayerst Laboratories (now Wyeth, acquired by Pfizer in 2009) in phase 1 trials in the early 2000s. Model Medicines teamed up with the Icahn School of Medicine at Mount Sinai and the school of medicine at UCSD to test the compound’s antiviral potential.