Non-cyclic dinucleotide STING agonists show promise as potential mpox treatment
Researchers demonstrated that non-cyclic dinucleotide (non-CDN) STING agonists can suppress mpox virus replication by bypassing a viral immune-evasion mechanism called poxin. The study found these compounds completely blocked virus replication in human immune cells and improved survival in infected mice. The findings suggest a novel therapeutic approach that could reduce the risk of antiviral resistance.
A preprint study published on bioRxiv describes how mpox virus uses a protein called poxin to disable the host immune response by degrading signaling molecules. Researchers found that non-cyclic dinucleotide STING agonists are resistant to poxin degradation and can activate immune signaling pathways even during active infection. In laboratory experiments using human primary fibroblasts and immune cells, these compounds completely blocked mpox and related orthopoxvirus replication. The mechanism involves activation of STING, IRF3, and STAT signaling pathways, triggering a distinctive immune response beyond standard interferon production. In vivo testing in mice infected with virulent mpox showed the compounds reduced illness signs and enhanced survival. The authors propose this represents a promising new therapeutic strategy by exploiting what they describe as an Achilles heel in the virus's immune-evasion strategy.
What's missing
The study is a preprint that has not undergone peer review. The authors do not discuss the stage of development, toxicity profile, pharmacokinetics, or timeline for potential clinical translation of these compounds. No information is provided about whether these agonists have been tested in other animal models or about their potential side effects in humans.
What different sources said
- bioRxivCenter
Non-cyclic dinucleotide STING agonists abrogate MPXV infection
Related
Gut Bacteria Enzyme Found to Break Down Heat-Processed Food Compounds, Producing Novel Biogenic Amines
Researchers have discovered that an enzyme in common gut bacteria can degrade N-epsilon-carboxymethyllysine (CML), a compound formed during thermal food processing, producing previously unknown biogenic amines. The enzyme, ornithine decarboxylase SpeC from enterobacteria, acts on CML and related modified lysine derivatives through a low-level 'underground' catalytic activity. This finding suggests a previously unrecognized communication axis between thermally processed dietary compounds and gut microbial physiology, with potential implications for host health.
Full-Length Gene Sequencing Reveals Two Distinct Bacterial Communities in Black-Legged Ticks Expanding Into Canada
Researchers used Oxford Nanopore full-length 16S rRNA gene sequencing to characterize the microbiome of Ixodes scapularis black-legged ticks collected in Nova Scotia, Canada, distinguishing between tick-adapted bacteria and environmentally acquired bacteria. The study comes as I. scapularis — the primary vector of Lyme disease — is rapidly expanding northward into Canada due to climate change. The findings suggest that environmentally derived bacteria in tick microbiomes are not mere contamination, which has implications for how tick microbiome data is collected and interpreted across surveillance studies.
Study Identifies Metabolic Link Between Cell Envelope Stress and Biofilm Formation in Bacteria
Researchers have discovered that the metabolite acetyl-CoA directly inhibits enzymes that degrade the bacterial signaling molecule c-di-GMP, connecting cell envelope biosynthesis stress to biofilm formation in Pseudomonas aeruginosa. The study found that sub-inhibitory concentrations of antibiotics targeting early peptidoglycan biosynthesis — but not other antibiotic classes — elevate c-di-GMP levels by reducing phosphodiesterase activity, with acetyl-CoA competing for the enzyme active site. Because the relevant enzyme domain is broadly conserved across bacterial species, this checkpoint mechanism may be widespread and could have implications for understanding antibiotic-induced biofilm responses.