{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T09:28:38Z","timestamp":1780824518163,"version":"3.54.1"},"reference-count":22,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"DTRA","doi-asserted-by":"crossref","award":["MCDC2001-010"],"award-info":[{"award-number":["MCDC2001-010"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. Government","award":["W15QKN-16-9-1002"],"award-info":[{"award-number":["W15QKN-16-9-1002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In human and non-human primates, filoviruses, e.g., Ebolaviruses, cause severe hemorrhagic fever for which there are few therapeutic options. While there are licensed vaccines and therapeutics for Ebola virus disease, there is no approved vaccine or treatment for other Ebola diseases. There is a need for broad-spectrum antivirals to treat Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV). We have previously demonstrated that probenecid, an FDA-approved drug with a safety profile spanning over 7 decades, is safe and effective in preventing the replication of influenza A viruses, SARS-CoV-2, and other RNA respiratory viruses, such as HMPV and RSV, both in vitro and in vivo. In this study, probenecid was shown to inhibit the replication of infectious EBOV, SUDV, and MARV in Vero E6 cells, with IC50 Values of 3 \u03bcM, 8 \u03bcM, and 13 \u03bcM, respectively. It also reduced plaque size in infected Vero cell lawns, suggesting reduced virus spread. These studies show that probenecid is an effective, broad-spectrum, host-directed antiviral drug.<\/jats:p>","DOI":"10.3390\/v18010043","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:25:51Z","timestamp":1766989551000},"page":"43","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Probenecid Against Filovirus Replication in Vero E6 Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Kendra","family":"Alfson","sequence":"first","affiliation":[{"name":"Texas Biomedical Research Institute, San Antonio, TX 78227, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-7683","authenticated-orcid":false,"suffix":"Jr.","given":"Ricardo","family":"Carrion","sequence":"additional","affiliation":[{"name":"Texas Biomedical Research Institute, San Antonio, TX 78227, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2924-9956","authenticated-orcid":false,"given":"Ralph A.","family":"Tripp","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7636-0542","authenticated-orcid":false,"given":"Chris","family":"Cirimotich","sequence":"additional","affiliation":[{"name":"Battelle Biomedical Research Center, West Jefferson, OH 43162, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2820-5983","authenticated-orcid":false,"given":"David E.","family":"Martin","sequence":"additional","affiliation":[{"name":"TrippBio, Inc., Jacksonville, FL 32256, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Munyeku-Bazitama, Y., Edidi-Atani, F., and Takada, A. (2024). Non-Ebola Filoviruses: Potential Threats to Global Health Security. Viruses, 16.","DOI":"10.3390\/v16081179"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-020-0147-3","article-title":"Ebola virus disease","volume":"6","author":"Jacob","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alfson, K.J., Avena, L.E., Beadles, M.W., Worwa, G., Amen, M., Patterson, J.L., Carrion, R., and Griffiths, A. (2018). Intramuscular Exposure of Macaca fascicularis to Low Doses of Low Passage- or Cell Culture-Adapted Sudan Virus or Ebola Virus. Viruses, 10.","DOI":"10.3390\/v10110642"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6773","DOI":"10.1128\/JVI.00649-15","article-title":"Particle-to-PFU ratio of Ebola virus influences disease course and survival in cynomolgus macaques","volume":"89","author":"Alfson","year":"2015","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Taki, E., Ghanavati, R., Navidifar, T., Dashtbin, S., Heidary, M., and Moghadamnia, M. (2023). Ebanga\u2122: The most recent FDA-approved drug for treating Ebola. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1083429"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1056\/NEJMoa1910993","article-title":"A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics","volume":"381","author":"Mulangu","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Garcia-Rodriguez, C., Mujica, P., Illanes-Gonzalez, J., Lopez, A., Vargas, C., Saez, J.C., Gonzalez-Jamett, A., and Ardiles, A.O. (2023). Probenecid, an Old Drug with Potential New Uses for Central Nervous System Disorders and Neuroinflammation. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061516"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jones, L.P., Martin, D.E., Murray, J., Sancilio, F., and Tripp, R.A. (2025). Probenecid Inhibits NLRP3 Inflammasome Activity and Mitogen-Activated Protein Kinases (MAPKs). Biomolecules, 15.","DOI":"10.3390\/biom15040511"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jones, L.P., Bergeron, H.C., Martin, D.E., Murray, J., Sancilio, F.D., and Tripp, R.A. (2024). Probenecid Inhibits Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase Mitogen-Activated Protein Kinase Pathways in Regulating Respiratory Syncytial Virus Response. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212452"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tripp, R.A., and Martin, D.E. (2023). Screening Drugs for Broad-Spectrum, Host-Directed Antiviral Activity: Lessons from the Development of Probenecid for COVID-19. Viruses, 15.","DOI":"10.3390\/v15112254"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Murray, J., Martin, D.E., Hosking, S., Orr-Burks, N., Hogan, R.J., and Tripp, R.A. (2024). Probenecid Inhibits Influenza A(H5N1) and A(H7N9) Viruses In Vitro and in Mice. Viruses, 16.","DOI":"10.3390\/v16010152"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Martin, D.E., Pandey, N., Chavda, P., Singh, G., Sutariya, R., Sancilio, F., and Tripp, R.A. (2023). Oral Probenecid for Nonhospitalized Adults with Symptomatic Mild-to-Moderate COVID-19. Viruses, 15.","DOI":"10.3390\/v15071508"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Murray, J., Bergeron, H.C., Jones, L.P., Reener, Z.B., Martin, D.E., Sancilio, F.D., and Tripp, R.A. (2022). Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication. Viruses, 14.","DOI":"10.21203\/rs.3.rs-1280404\/v1"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tripp, R.A., and Martin, D.E. (2022). Repurposing Probenecid to Inhibit SARS-CoV-2, Influenza Virus, and Respiratory Syncytial Virus (RSV) Replication. Viruses, 14.","DOI":"10.3390\/v14030612"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Jones, L.P., Martin, D.E., and Tripp, R.A. (2025). The MAPK Response to Virus Infection Is Modified by Probenecid. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47040246"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bergeron, H.C., Crabtree, J., Nagy, T., Martin, D.E., and Tripp, R.A. (2024). Probenecid Inhibits Human Metapneumovirus (HMPV) Replication In Vitro and in BALB\/c Mice. Viruses, 16.","DOI":"10.3390\/v16071087"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1053\/j.spid.2005.05.001","article-title":"Outbreak of Marburg hemorrhagic fever in Angola: A review of the history of the disease and its biological aspects","volume":"16","author":"Ligon","year":"2005","journal-title":"Semin. Pediatr. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1080\/22221751.2022.2086072","article-title":"Natural history of Sudan ebolavirus infection in rhesus and cynomolgus macaques","volume":"11","author":"Woolsey","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.coviro.2019.03.001","article-title":"Current status of small molecule drug development for Ebola virus and other filoviruses","volume":"35","author":"Edwards","year":"2019","journal-title":"Curr. Opin. Virol."},{"key":"ref_20","first-page":"eadk6176","article-title":"Oral administration of obeldesivir protects nonhuman primates against","volume":"383","author":"Cross","year":"2024","journal-title":"Sudan Ebolavirus Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"eadw0659","DOI":"10.1126\/sciadv.adw0659","article-title":"The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection","volume":"11","author":"Woolsey","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zumbrun, E.E., Garvey, C.B., Wells, J.B., Lynn, G.C., Van Tongeren, S.A., Steffens, J.T., Wetzel, K.S., Wetzel, D.L., Esham, H.L., and Garza, N.L. (2024). A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques. Viruses, 16.","DOI":"10.3390\/v16121934"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/1\/43\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T05:12:25Z","timestamp":1767244345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/1\/43"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["v18010043"],"URL":"https:\/\/doi.org\/10.3390\/v18010043","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]}}}