Researchers from TWINCORE, a joint venture of the Helmholtz Center for Infection Research and Hannover Medical School, have made a groundbreaking discovery that could lead to broad-spectrum antiviral treatments.
Led by Prof. Frank Peßler, the team published their findings in the journal PLOS Pathogens.
A Dual Mechanism for Virus Inhibition
The team focused on the body’s own molecule, itaconic acid, and its pharmacologically optimized variant, 4-octyl itaconate.
They found that 4-octyl itaconate activates a signaling pathway controlled by the protein NRF2, which in turn controls various protective and defense mechanisms in human cells.
Surprisingly, this substance also directly inhibits viral replication, even when NRF2 is absent.
Unveiling the Key Mechanism
Initial experiments revealed that 4-octyl itaconate obstructs the transport of proteins and nucleic acids from the cell nucleus, a crucial step that many viruses rely on for replication.
When compared to a cancer drug (selinexor) known to block this transport channel, both substances effectively inhibited the replication of influenza viruses.
“We were quite astonished,” says Prof. Frank Peßler. “We had obviously been studying the right active ingredient all along, but only now got onto the trail of the decisive mechanism of action.”
Broad-Spectrum Efficacy
This discovery opens new avenues for developing antiviral therapies effective against a variety of viruses, from influenza and SARS-CoV-2 to rabies. “The next pandemic is bound to come,” adds Peßler.
“And wouldn’t it be nice to have a pill that could help people quickly and curb the spread early—even before we know exactly which virus it is?”
Towards a Rapid Adaptation of Therapy
The research is particularly promising because an inhibitor of this transport channel has already been approved as a drug.
This speeds up the prospect of adapting existing treatments for a range of viral infections.
Peßler’s team is also working on optimizing itaconic acid variants to have both virus-inhibiting and cell-protecting effects, leveraging the fact that itaconic acid naturally occurs in humans, which could minimize side effects.
A Promising Step Forward
This research represents a significant step toward a universal antiviral treatment.
By targeting a mechanism essential for a wide variety of viruses, the researchers are closer to developing a treatment capable of inhibiting viral infections on a broad scale.
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The study was published in PLOS Pathogens.
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