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Monkeypox Virus Is Inhibited by Nucleoside Analogues Including the Acyclic Phosphonates Adefovir and Tenofovir In
Jasper Lee1,2, Huanchun Zhang1,2, Emerson Ailidh Boggs1,2
1Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Center for ViroScience and Cure, Atlanta, Georgia, USA.
Journal of Medical Virology
|October 25, 2025
Summary
New antivirals are needed for mpox (monkeypox virus) due to drug resistance. Adefovir dipivoxil and tenofovir alafenamide show potent activity against orthopoxviruses with low toxicity, offering promising treatment options.
Area of Science:
- Virology
- Infectious Diseases
- Drug Discovery
Background:
- Mpox (monkeypox virus) outbreaks necessitate novel antiviral therapies.
- Current treatments face challenges of drug resistance and toxicity.
- There is an unmet need for effective and safe treatments for orthopoxvirus infections.
Purpose of the Study:
- To identify novel antiviral compounds against mpox and other orthopoxviruses.
- To evaluate the efficacy and safety of potential drug candidates.
- To establish screening assays for antiviral drug discovery.
Main Methods:
- Developed in vitro screening assays using recombinant vaccinia virus and mpox virus (MPXV).
- Measured the antiviral potency of various compounds.
- Assessed compound toxicity in cellular models.
Main Results:
- Adefovir dipivoxil and tenofovir alafenamide demonstrated potent anti-orthopoxvirus activity.
- These compounds exhibited low toxicity profiles.
- The screening assays successfully identified effective antiviral agents.
Conclusions:
- Nucleoside analogues are promising candidates for repurposing as antivirals against poxviruses.
- Adefovir dipivoxil and tenofovir alafenamide warrant further investigation for mpox treatment.
- The developed assays provide a foundation for future high-throughput screening and resistance studies.
