Oral Antiviral Cocktail Blocks Enterovirus Replication in Lab Tests
Scientists identified an oral antiviral cocktail that blocks enterovirus replication in human cell and organoid models.
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Enteroviruses are a large group of RNA viruses that can cause a range of conditions, from the common cold to more serious illnesses such as meningitis, poliomyelitis and type 1 diabetes. Although more than 100 distinct enterovirus types have been identified, there are no broad-spectrum antiviral treatments or vaccines approved to combat them.
Enterovirus
A genus of single-stranded RNA viruses in the Picornaviridae family. These viruses are transmitted via the fecal-oral route and respiratory secretions. They are known to cause a wide range of illnesses, from minor febrile infections to severe neurological conditions.One reason for the lack of treatment options is that most infected individuals recover without medical intervention. However, severe cases – especially among children – highlight the need for therapies that can target multiple strains.
“Enteroviruses pose a significant global health problem,” said Erlend Ravlo.
Identifying a viable target
Researchers at the Norwegian University of Science and Technology (NTNU), in collaboration with colleagues across Europe, have tested drug combinations that inhibit viral replication in human cells and mini-organ cultures. Viral replication, the process by which viruses copy themselves inside host cells, offers a strategic point of intervention for potential treatments.
Mini-organ (organoid)
A three-dimensional cell culture system that mimics the structure and function of actual organs. Organoids are derived from stem cells and are used in research to model diseases, test drugs and study developmental biology.Viral replication
The process by which viruses reproduce within a host cell. This cycle includes attachment to the host, entry, replication of genetic material, assembly of new viral particles and release from the cell. Inhibiting this process can halt the spread of infection.The team identified two promising combinations that showed efficacy in blocking replication in vitro. One of these includes three oral medications – pleconaril, AG7404 and mindeudesivir. Each of these drugs has previously been tested in humans for safety, and the combination did not negatively affect glucose or insulin levels in pancreatic cells. It also did not disrupt heart rate in cardiac mini-organs.
Towards a practical therapy
The researchers initially explored 12 antiviral agents with known broad-spectrum potential, testing both individual compounds and combinations across various viral types in cell culture. One earlier successful combination included pleconaril, rupintrivir and remdesivir. However, its use was limited by formulation challenges, as rupintrivir and remdesivir cannot be administered together in a single oral dose.
To address this, the team replaced rupintrivir and remdesivir with AG7404 and mindeudesivir. This revised combination retained antiviral activity while offering a more practical oral dosing regimen.
Next steps
Although these findings are encouraging, they are limited to laboratory models. The combination has not yet been tested in humans or in animal models beyond cell cultures and organoids. Further research is required to validate its safety and efficacy in clinical settings and across multiple enterovirus strains.
Reference: Ravlo E, Ianevski A, Schjølberg JO, et al. Synergistic combination of orally available safe-in-man pleconaril, AG7404, and mindeudesivir inhibits enterovirus infections in human cell and organoid cultures. Cell Mol Life Sci. 2025;82(1):57. doi: 10.1007/s00018-025-05581-4
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