Anti-Orthopoxvirus Drugs Show Promise Against Lumpy Skin Disease Virus
New research identifies existing antiviral drugs that may help combat lumpy skin disease in cattle by shutting down viral DNA replication.
Lumpy skin disease (LSD) is an emerging, highly contagious viral disease of cattle that continues to spread across Africa, Europe, and Asia, causing massive economic losses worldwide. Despite its global impact, there are currently no approved antiviral drugs for lumpy skin disease virus (LSDV), leaving vaccination and culling as the primary control strategies.
A new 2026 study published in PLoS Pathogens offers hope by identifying repurposable antiviral drugs that significantly inhibit LSDV replication — and one compound in particular stands out.
Why Lumpy Skin Disease Is So Hard to Treat
LSDV is a large DNA virus in the Poxviridae family that replicates in the cytoplasm of infected cells using its own viral DNA polymerase. This makes the virus biologically complex and difficult to target with conventional antivirals. While vaccines are essential for outbreak control, they can carry risks, including adverse reactions and viral recombination.
Given the urgent need for treatments, the researchers turned to drug repurposing — screening existing antiviral compounds that are already used against related poxviruses.
A New High-Tech Screening Tool for LSDV
To accelerate drug discovery, the researchers engineered a recombinant LSDV containing two reporter genes (mCherry and luciferase). This allowed them to:
Track viral replication in real time
Accurately measure viral activity
Perform high-throughput drug screening
Importantly, the modified virus behaved just like the wild-type virus, making it a reliable testing platform.
Six Existing Drugs Block LSDV Replication
Using this screening system, the team tested an anti-orthopoxvirus drug library and identified six compounds that strongly inhibited LSDV replication while maintaining low toxicity:
Cytarabine (AraC)
Vidarabine (AraA)
Idoxuridine (IDU)
Fialuridine (FIAU)
Ribavirin (RBV)
Enrofloxacin (ENR)
All six drugs reduced viral replication by more than 90% in laboratory cell cultures.
Cytarabine (AraC) Emerges as the Top Candidate
Among the six, cytarabine (AraC) demonstrated the most compelling antiviral profile:
Potently blocked viral DNA synthesis
Completely prevented late viral gene expression
Arrested the viral replication cycle early
Caused minimal host cell toxicity
Did not rely on inducing apoptosis or cell death to stop the virus
Time-of-addition experiments confirmed that AraC works after viral entry, directly targeting the replication phase rather than virus attachment or penetration.
How AraC Stops the Virus
Mechanistic and structural analyses revealed that AraC likely binds directly to the LSDV DNA polymerase, preventing the virus from copying its genome. Without viral DNA synthesis:
Late viral genes are never activated
Structural proteins are not produced
New virus particles cannot form
Even though similar binding sites exist in bovine DNA polymerase, host cells were able to recover DNA synthesis over time, limiting toxicity.
Why This Matters for Global Cattle Health
This study highlights viral DNA polymerase as a key therapeutic target for LSDV and demonstrates that existing antiviral drugs may be rapidly repurposed to combat this disease. Given AraC’s established clinical availability and safety data, it represents a particularly promising lead compound.
Clinical Takeaway for Veterinarians
No approved antiviral treatments currently exist for lumpy skin disease
Drug repurposing may offer faster, safer treatment options
Cytarabine shows strong in-vitro efficacy against LSDV
Further in vivo and clinical studies are needed before field use
Bottom Line
This study provides a major step forward in LSD research, offering a potential path toward antiviral therapy for a disease that continues to devastate cattle industries worldwide. While vaccines remain critical, targeted antivirals like cytarabine could one day reduce disease severity, mortality, and economic loss during outbreaks.
