Viral RNA relies on an enzyme to replicate, which offers up a target to protect against a range of pathogens
Juan Gaertner/Science Photo Library/Alamy
A single drug has been found to inhibit a range of common viruses in lab studies, including coronaviruses, respiratory syncytial virus (RSV), norovirus, and influenza and hepatitis viruses. It will be tested in a clinical trial next year, raising hopes that the pill could one day be taken at home to relieve unpleasant symptoms or even limit infections if there were another viral pandemic.
“As far as we can tell, this is the first drug that’s ever demonstrated activity across all these viral families,” says Daniel Haders, co-founder of Model Medicines, the California-based company leading its development. If it is approved, Haders envisages it being a pill that people could take if, for example, they have a flu-like illness but don’t know if it is influenza, covid-19, RSV or something else.
The drug was originally developed as a breast cancer treatment named ERA-923, but it was abandoned in the early 2000s after showing little benefit in clinical trials. Now, an AI drug-discovery platform developed by Haders and his colleagues has figured out that the forgotten medicine may inhibit a range of viruses via an unrelated mechanism.
The platform was tasked with finding a drug that could block a viral enzyme called RNA-dependent RNA polymerase, which many viruses use to copy their genomes and replicate. It specifically looked for drugs that could bind to a section of the enzyme called the Thumb-1 domain, after identifying that this site is conserved across multiple viruses. “We wanted to find a biological chokepoint – a place where a single drug against a single target could solve dozens of diseases,” says Haders.
By mining data from old papers and patents, the AI named ERA-923 as a potential candidate that could bind to the Thumb-1 domain and thus block viral replication. “Like how OpenAI and Anthropic have downloaded all digital human knowledge, we’ve done the same thing for all of chemistry, biology and clinical pharmacology,” says Haders. He has been applying computational methods to drug design since his PhD research 20 years ago, but says the AI tools available now are “a million times better”.
To test the AI’s prediction, the researchers measured the activity of the drug, renamed MDL-001, against a range of viruses in infected cells in a lab. They found that it inhibited the influenza A and B viruses, a number of coronaviruses that cause common colds or covid-19, RSV (which causes flu-like symptoms and can be severe in babies), norovirus (also known as the winter vomiting bug) and hepatitis B, C and D, which damage the liver.
MDL-001 also helped treat covid-19 in mice, lowering levels of the underlying virus in their lungs and reducing their weight loss from the illness. It had similar efficacy in mice with hepatitis B and C. Haders will present the results at the Congress of the European Society of Clinical Microbiology and Infectious Diseases in Munich, Germany, in mid-April.
Peter White at the University of New South Wales in Australia is sceptical, since other drugs that have been developed to target the Thumb-1 domain only inhibit hepatitis C, not other viruses. But Model Medicines claims that MDL-001 has a different docking mode that allows it to work across multiple viruses. Daniel Rawle at QIMR Berghofer Medical Research Institute in Brisbane, Australia, also notes that “most antivirals that work in vitro fail in vivo”.
Model Medicines is now planning a clinical trial of MDL-001, which is scheduled to begin early next year. The first step will be to make sure it is safe, although past trials in people with breast cancer have found that it has minimal side effects.
At the moment, viral illnesses are a major burden on well-being and productivity, because people often have to take time off work when they or their children become sick with them. It would be a game changer if these conditions could be rapidly treated with a short course of a multipurpose antiviral pill at home, says Haders. MDL-001 may also be useful in the case of future pandemics of novel coronaviruses or influenza viruses, he says.
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