{
  "abstract": "Viral respiratory infections remain a major and recurrent public health threat. Among them, influenza viruses are responsible for ⁓500,000 deaths worldwide and a high economic burden. The recurrent threat of emerging zoonotic or pandemic viruses worsens this scenario, being SARS-CoV-2 and the millions of COVID-19 deaths the most recent example. The rapid evolution of circulating influenza and SARS-CoV-2 viruses allows the emergence and dissemination of variant strains carrying mutations resulting in suboptimal vaccine protection and/or reduced efficacy of current limited therapeutic arsenal. In this context, host-targeted approaches constitute a promising antiviral strategy aiming to achieve broad-spectrum activity and mitigate the emergence of viral resistance against classic direct acting antivirals. Here, we demonstrated that diltiazem, a calcium channel blocker currently used to treat angor, induces an ISG expression profile characteristic of an antiviral cellular state mainly driven by IFN-λ. We then evaluated the potential of the diltiazem-baloxavir combination against Influenza A wild-type and the PA I38T resistant strain in cell culture and human airway epithelia (HAE). We analogously evaluated the diltiazem-molnupiravir combination against SARS-CoV-2, including variants of concern. Our results demonstrate the broad-spectrum antiviral activity of diltiazem against Influenza A viruses, including resistant strains, as well as the capacity to potentiate the antiviral effect of baloxavir. The diltiazem-molnupiravir combination further reduced viral production and protected the integrity of HAE infected with SARS-CoV-2. This study highlights the major interest of combining direct acting and host-targeted agents as a promising strategy against circulating and emerging viruses.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Blandine Padey"
    },
    {
      "name": "Clément Droillard"
    },
    {
      "name": "Victoria Dulière"
    },
    {
      "name": "Julien Fouret"
    },
    {
      "name": "Claire Nicolas De Lamballerie"
    },
    {
      "name": "Cédrine Milesi"
    },
    {
      "name": "Emilie Laurent"
    },
    {
      "name": "Pauline Brun"
    },
    {
      "name": "Aurélien Traversier"
    },
    {
      "name": "Thomas Julien"
    },
    {
      "name": "Olivier Terrier"
    },
    {
      "name": "Manuel Rosa-Calatrava"
    },
    {
      "name": "Andrés Pizzorno"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cxjaa2fn85gq9.bib",
  "cited_by": 5,
  "doi": "10.1016/j.antiviral.2025.106138",
  "fulltext_url": null,
  "id": "cxjaa2fn85gq9",
  "issns": [
    "0166-3542"
  ],
  "landing_url": "https://hal.science/hal-04981182v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "hal",
      "1.sdv.mp"
    ],
    [
      "hal",
      "1.sdv.sp"
    ],
    [
      "hal",
      "2.sdv.mhep.mi"
    ],
    [
      "hal",
      "2.sdv.mhep.psr"
    ],
    [
      "hal",
      "2.sdv.mp.vir"
    ],
    [
      "hal",
      "2.sdv.sp.pharma"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W4408148117",
  "pdf_url": "https://hal.science/hal-04981182/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": "Elsevier Masson",
  "ris": "https://research.draconitic.com/paper/cxjaa2fn85gq9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:47Z",
      "native_id": "hal-04981182",
      "source": "hal",
      "url": "https://hal.science/hal-04981182v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.mp",
      "subfield": "microbiology"
    },
    {
      "field": "medicine",
      "origin": "hal:2.sdv.mhep.mi",
      "subfield": "infectious-disease"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.sp",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Host-targeted repurposed diltiazem enhances the antiviral activity of direct acting antivirals against Influenza A virus and SARS-CoV-2",
  "title_text": "Host-targeted repurposed diltiazem enhances the antiviral activity of direct acting antivirals against Influenza A virus and SARS-CoV-2",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:47Z",
  "url": "https://research.draconitic.com/paper/cxjaa2fn85gq9",
  "venue": "Antiviral Research",
  "versions": []
}