Two peptides designed to target a newly discovered RNA-unwinding function of the rabies virus effectively blocked viral replication in cells.
First-ever targetFirst RNA-unwinding activity identified in any rhabdovirus, and first peptide-based inhibitors shown to block rabies replication
What the researchers found
Researchers discovered that the rabies virus phosphoprotein (RABV-P) has previously unknown RNA-unwinding activities — both helicase-like (energy-dependent) and chaperone-like (energy-independent). This is the first such activity identified in any rhabdovirus.
Critically, two designed peptides (P90 and P110) targeting the protein's oligomerization domain effectively inhibited rabies virus replication in cells, demonstrating a new therapeutic strategy against this nearly 100% fatal disease.
Why it matters
Rabies kills approximately 59,000 people annually and is nearly 100% fatal once symptoms appear. There are no effective antivirals. Discovering a new druggable target on the rabies virus — and showing that peptides can block it — opens a completely new therapeutic approach for one of the deadliest known viruses.
The numbers in context
2 peptides designed (P90, P110) · First RNA-unwinding activity in Rhabdoviridae · C-terminal domain + COD required · Effective cell-based inhibition
How the study worked
Laboratory study combining biochemical characterization of RABV phosphoprotein's RNA-unwinding activities with peptide inhibitor design. RNA duplex-unwinding and annealing assays characterized the enzymatic activities. Two peptides targeting the central oligomerization domain (COD) were designed and tested for antiviral activity in cell-based rabies virus replication assays.
Who was studied
Not applicable (in vitro and cell-based virology study)
What this study cannot tell us
Entirely in vitro and cell-based — no animal model testing. Peptide stability, delivery to the nervous system (where rabies replicates), and in vivo efficacy were not assessed. Rabies virus primarily infects neurons, which are challenging drug targets. The peptides' effectiveness against different rabies strains was not evaluated.
How to read the evidence
This is a discovery-stage laboratory study combining fundamental virology with initial peptide inhibitor development. While scientifically significant as a first-in-class finding, it is far from clinical application.
When this study was published
Published in 2026, this represents cutting-edge virology research that could open new antiviral strategies against one of the world's deadliest viruses.
The bigger picture
Despite rabies being one of the oldest known diseases, there are still no effective antivirals — only prevention through vaccination. This discovery of a druggable enzymatic activity in the rabies virus, combined with proof-of-concept peptide inhibitors, represents the first step toward changing this. The approach could also apply to related rhabdoviruses affecting both humans and animals.
Questions still open
- Can these peptides cross the blood-brain barrier to reach rabies-infected neurons?
- Would these peptides be effective as post-exposure treatment before or after symptom onset?
- Does the RNA-unwinding activity and COD targeting approach work against other rhabdoviruses?
Common questions
Why is it so hard to treat rabies?
How do the P90 and P110 peptides work against rabies?
Read the original research
Rabies lyssavirus phosphoprotein possesses RNA duplex-unwinding activities.
Molecular therapy. Nucleic acids, 37(1), 102863
Citation
Mu, Jingfang; Wang, Caiqian; Shu, Ting; Xiong, Xiaobei; Ren, Yujie; Gong, Rui; Zhao, Ling; Zhou, Xi. (2026). Rabies lyssavirus phosphoprotein possesses RNA duplex-unwinding activities.. Molecular therapy. Nucleic acids, 37(1), 102863. https://doi.org/10.1016/j.omtn.2026.102863