New Broad-Spectrum Antiviral Candidate Identified Against Enteroviruses

Researchers from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) have identified a promising antiviral compound, GW406108X, that inhibits a range of enteroviruses, including Enterovirus D68 (EV-D68), an emerging respiratory virus linked to severe illness and acute flaccid myelitis, a condition that can cause paralysis. The findings, published in Acta Pharmaceutica Sinica B, could support broad-spectrum treatments against enteroviruses, which currently lack effective antivirals.

The study was led by Associate Professor Justin Chu of the Department of Microbiology and Immunology and Infectious Diseases Translational Research Program at NUS Medicine. Unlike many antivirals that attack the virus directly, the compound targets a process inside the infected cell, Chu said, aiming to block the host cell machinery the virus exploits.

To find potential treatments, the team screened 7,986 compounds from nine drug libraries. GW406108X cut EV-D68 levels by about 1,000-fold in laboratory tests, and was also effective against a second EV-D68 strain and Rhinovirus A16, and showed activity against dengue virus serotype 2. It works by blocking two proteins, ULK1 and ULK2, which help start autophagy, a process cells use to recycle damaged material but which enteroviruses hijack to multiply. This reduced the structures the virus uses to copy its genetic material and release new particles. EV-D68 stayed sensitive to it after 18 rounds of testing, though its resistance potential needs further study.

In preclinical studies, no toxic effects were observed at the dose tested. The untreated infected control group had an 83.3% mortality rate, while groups receiving GW406108X recorded 100% survival and showed milder signs of infection. At the higher dose tested, virus levels in the lungs were about 80% lower than in the untreated control group.

The researchers stressed that the findings remain at an early, preclinical stage. Further studies are needed to optimize the compound and evaluate its safety, dosage and pharmacological properties before it can be considered for human clinical trials.