New drug combination shows potential to treat enteroviruses

Enteroviruses are a widespread and diverse group of viruses responsible for a broad range of diseases. From the common cold to more severe conditions such as meningitis, polio, and even type 1 diabetes. With over 100 different types identified, these viruses infect millions of people globally each year. Despite their abundance, there is still no approved general treatment or vaccine available to combat them. 

Now, researchers at the Norwegian University of Science and Technology (NTNU), along with collaborators across Europe, are making steps to rectify that. Their research has lead to the discovery of a promising combination of drugs that effectively halts the replication of these viruses in human cells and laboratory-grown mini-organs. By targeting the virus’s ability to replicate inside infected cells, the scientists believe they’ve found a critical point of intervention. 

A breakthrough in the lab 

“Enteroviruses pose a significant global health problem,” says Dr Erlend Ravlo, a PhD research fellow at the Norwegian University of Science and Technology (NTNU)’s Department of Clinical and Molecular Medicine. Yet the absence of a universal treatment may be partly because many patients recover without medical intervention. However, in severe cases, particularly in children, illness can escalate rapidly, underscoring the urgent need for broad-spectrum antiviral therapies. 

“We have identified a combination of drugs that appears to prevent enteroviruses from replicating,” explains Aleksandr Ianevski from NTNU’s Department of Clinical and Molecular Medicine. 

Though not yet tested in humans, the drug combination has demonstrated encouraging results in preclinical studies. The corresponding authors of the study, Professors Denis Kainov and Magnar Bjørås, highlight that these findings mark a significant milestone, though further research will be needed. 

An oral solution with minimal side effects 

The key drug combination of pleconaril, AG7404, and mindeudesivir has several advantages. Firstly, all three are already familiar to medical professionals. Secondly, and most importantly, they can be administered orally as a single pill. 

“These drugs have been tested individually on humans, and the combination shows promise without harmful side effects on pancreatic or cardiac cells,” notes Kainov. This is particularly reassuring for individuals at risk of diabetes or heart conditions, as the combination does not disrupt glucose levels or heart rhythms in laboratory tests. 

Bjørås adds, “This cocktail of medicines is really promising.” 

The road to the right formula 

Arriving at this combination was not a quick process. The NTNU team systematically tested 12 antiviral agents, both individually and in various combinations, against a range of enteroviruses in lung cells and intestinal organoids. 

One earlier, effective mixture included pleconaril, rupintrivir, and remdesivir. However, because rupintrivir and remdesivir cannot be easily combined into a single pill, the team switched their attention to AG7404 and mindeudesivir, which achieved similar effectiveness with added practicality. 

“Our studies show great potential for finding broad-spectrum treatment methods against enteroviruses,” says Kainov. 

What comes next? 

While the results are promising, the researchers say that more work lies ahead. Clinical trials and further testing across a broader range of enteroviruses are essential before this treatment can be brought to patients. 

Nonetheless, this development represents a significant development in tackling a longstanding gap in viral treatment. If successful in human trials, this drug combination could transform the way we treat enterovirus infections, offering a reliable, accessible option for millions worldwide.