Evidence map›Paper›PMID 39861882›Full record

ArticleViruses2025

Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.

Haydar Witwit, Beatrice Cubitt, Roaa Khafaji, Esteban M Castro, Miguel Goicoechea, Maria M Lorenzo, Rafael Blasco, Luis Martinez-Sobrido, Juan C de la Torre

Abstract read
In one paragraph

Article in Viruses, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Haydar WitwitDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-0174-8454
Beatrice CubittDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-8048-410X
Roaa KhafajiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Esteban M CastroTexas Biomedical Research Institute, San Antonio, TX 78227, USA.
Miguel GoicoecheaDivision of Infectious Diseases, Scripps Health, San Diego, CA 92103, USA.
Maria M LorenzoDepartamento de Biotecnología, INIA CSIC, 28040 Madrid, Spain.
Rafael BlascoDepartamento de Biotecnología, INIA CSIC, 28040 Madrid, Spain.ORCID 0000-0002-8819-5767
Luis Martinez-SobridoTexas Biomedical Research Institute, San Antonio, TX 78227, USA.ORCID 0000-0001-7084-0804
Juan C de la TorreDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.ORCID 0000-0002-8171-8115

Funding

Scripps Clinical and Translational Science HubUM1TR004407 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI Eric Jeffrey Topol · 2023 to 2026
$24.2M
NCATS NIH HHS UM1 TR004407UM1 TR004407 Pilot Award 2023 UM1 TR004407 Pilot
6 · The paper itself

Abstract

The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088. Both MMF and IMP-1088 drugs exhibited strong dose-dependent antiviral activity against VACV and mpox, and potent synergistic effects in conjunction with TPOXX. Our findings support combination therapy of direct-acting (TPOXX) and host-targeted (MMF and IMP-1088) antivirals as a promising approach to treat mpox and prevent the emergence and spread of TPOXX-resistant MPXV variants.

Indexed as

Antiviral AgentsDrug RepositioningDrug Resistance, ViralDrug SynergismDrug Therapy, CombinationIsoindolesMonkeypox virusBenzamidesChlorocebus aethiopsHumansMpox, MonkeypoxPhthalimidesVaccinia virusAntiviral AgentsBenzamidesIsoindolesPhthalimidestecovirimatantiviraldrug repurposingdrug synergistic interactionsIMP-1088monkeypoxmpoxmycophenolate mofetilmyristoylationPoxviridaetecovirimatTPOXXvaccinia virusVACV

Identifiers

PMID39861882
PMCPMC11769280

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.