RT Journal Article
T1 Antiviral Activity of the Acyclic Nucleoside Phosphonate Prodrug LAVR-289 against Poxviruses and African Swine Fever Virus
A1 Marcheteau, Elie
A1 Mosca, Estelle
A1 Frenois Veyrat, Gaelle
A1 Kappler-Gratias, Sandrine
A1 Boutin, Laetitia
A1 Top, Sokunthea
A1 Mathieu, Thomas
A1 Colas, Cyril
A1 Favetta, Patrick
A1 Garnier, Tony
A1 Barbe, Peggy
A1 Keck, Mathilde
A1 Gillet, Daniel
A1 Mas Zubiri, Alicia
A1 Alejo, Ali
A1 Yu, Yinyi
A1 Toth, Karoly
A1 Abate, Getahun
A1 Roy, Vincent
A1 Skerry, Janet
A1 Wetzel, Kelly S
A1 Shamblin, Joshua D
A1 Golden, Joseph W
A1 Panchal, Rekha G
A1 Mucker, Eric M
A1 Mudhasani, Rajini
A1 Agrofoglio, Luigi A
A1 Iseni, Frederic
A1 Gallardo, Franck
AB Poxviruses are double-stranded DNA viruses including relevant zoonotic pathogens with high morbidity and potential biological warfare threats. Although African swine fever virus belongs to the Asfarviridae family and is not strictly classified as a Poxviridae member, both fall within the same class of Pokkesviricetes that replicate in the cytoplasm. Among compounds targeting these viruses, acyclic nucleoside phosphonate (ANP) prodrugs are promising inhibitors of viral DNA polymerases. However, some limitations related to their toxicity and the rapid emergence of resistance highlight the need for new antiviral molecules. In this study, we tested a new ANP called LAVR-289. This product effectively inhibits viral replication by targeting a specific domain in the poxvirus DNA polymerase. Using monkeypox virus models, the subcutaneous or oral administration of LAVR-289 demonstrated protective efficacy in infected animals without toxicity. Its in vivo half-life, long on-the-shelf stability and broad-spectrum efficacy make LAVR-289 a promising candidate for further development and stockpiling as a medical countermeasure against dsDNA virus outbreaks. LAVR-289 can be positioned in the context of recurrent viral epidemics, bioterrorism risk, and the emergence of resistant strains in the population
PB American Chemical Society
YR 2025
FD 2025
LK https://hdl.handle.net/20.500.14352/120904
UL https://hdl.handle.net/20.500.14352/120904
LA eng
NO Marcheteau, E., Mosca, E., Frenois-Veyrat, G., Kappler-Gratias, S., Boutin, L., Top, S., Mathieu, T., Colas, C., Favetta, P., Garnier, T., Barbe, P., Keck, M., Gillet, D., Mas, A., Alejo, A., Yu, Y., Toth, K., Abate, G., Roy, V., Skerry, J., … Gallardo, F. (2025). Antiviral Activity of the Acyclic Nucleoside Phosphonate Prodrug LAVR-289 against Poxviruses and African Swine Fever Virus. ACS infectious diseases, 10.1021/acsinfecdis.5c00169. Advance online publication. https://doi.org/10.1021/acsinfecdis.5c00169
NO Author ContributionsConceptualization: R.M., L.A.A., F.G., and F.I.; Experiments:E.M., E.Mo., G.F.V., S.K.-G., L.B., S.T., T.M., C.C., P.F., T.G.,P.B., M.K., D.G., A.M., A.A., Y.Y., K.T., G.A., V.R., J.S., K.S.W.,S.D.J., G.W.J., R.G.P., E.M.M., R.M., F.I., and FG.; Super-vision: F.G. and F.I.; Writing�review and editing: F.G., R.M.,F.G., M.K., L.A.A., E.M.M., K.T., G.A., and F.I.; Fundingacquisition: L.A.A., F.G., and F.I. All authors have read andagreed to the published version of the manuscript
NO Division of Microbiology and Infectious Diseases
NO Region Centre Val de Loire (APR-IR FINALS)
NO Centre National de la Recherche Scientifique (CNRS)
NO European Commission
NO United States Department of Health & Human Services National Institutes of Health (NIH) - USA
NO United States Department of Health & Human Services National Institutes of Health (NIH) - USA
DS Docta Complutense
RD 20 dic 2025