LAVR-289, an Acyclo-Nucleoside Phosphonate, Has Broad-Spectrum Activity against Herpesviruses
Human herpesviruses are large dsDNA viruses that primarily cause opportunistic infections in healthy adults but can trigger life-threatening infections in immunocompromised patients. Previously, antivirals have been developed against a variety of herpesviruses; these include acyclovir for herpes simplex viruses (HSV1 and 2) and ganciclovir and letermovir for human cytomegalovirus (hCMV). However, broad-spectrum inhibitors of herpesvirus infections are still lacking. Here we report the efficacy of LAVR-289, a new acyclic nucleoside analogue, on a broad range of herpesviruses of human and animal origin. LAVR-289 displays nanomolar efficacy <i>in vitro</i>, is active on viral strains resistant to gold-standard antivirals and is efficacious <i>ex vivo</i> on reconstituted human skin infected with HSV1. In addition, the activity of LAVR-289 against poxviruses and adenoviruses is an indication of its potential for the management of opportunistic virus infections in immunocompromised patients.
Authors
- Vincent Roy
- Sandrine Kappler‐Gratias
- Charlotte Quentin-Froignant (ORCID: https://orcid.org/0000-0003-2393-8408)
- Franck Gallardo (ORCID: https://orcid.org/0000-0001-9341-826X)
- David Boutolleau
- Luigi A. Agrofoglio (ORCID: https://orcid.org/0000-0002-6083-0810)
- Elie Marcheteau (ORCID: https://orcid.org/0000-0001-6630-9682)
- José Luís Fernández (ORCID: https://orcid.org/0000-0002-2985-7169)
- Virginie Garcia (ORCID: https://orcid.org/0000-0002-9761-7036)
Institutions
- Université d'Orléans (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Sorbonne Université (FR)
- Centre de Recherches en Cancérologie de Toulouse (FR)
- Centre National pour la Recherche Scientifique et Technique (CNRST) (MA)
- Assistance Publique – Hôpitaux de Paris (FR)
- Pitié-Salpêtrière Hospital (FR)
- Institut Pierre Louis d‘Épidémiologie et de Santé Publique (FR)
- Institut de Chimie Organique et Analytique (FR)
- Laboratoire Médiations (FR)
Publication Details
- Journal
- ACS Infectious Diseases
- Published
- 2025-05-17
- DOI
- https://doi.org/10.1021/acsinfecdis.5c00171
- Citations
- 1
- Primary Topic
- Cytomegalovirus and herpesvirus research
- Type
- article
- Field-Weighted Citation Impact
- 1.35
Funders
- Agence Nationale de la Recherche
- Centre National de la Recherche Scientifique
- Université d'Orléans
- European Regional Development Fund