{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:13:35Z","timestamp":1788261215857,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008065","name":"Georgia Research Alliance","doi-asserted-by":"publisher","award":["not available"],"award-info":[{"award-number":["not available"]}],"id":[{"id":"10.13039\/100008065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB\/c mice. The studies showed that nanomolar concentrations of all probenecid regimens prevent RSV strain A and B replication in vitro and RSV strain A in vivo, representing a potential prophylactic and chemotherapeutic for RSV.<\/jats:p>","DOI":"10.3390\/v14050912","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T22:20:20Z","timestamp":1651098020000},"page":"912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication"],"prefix":"10.3390","volume":"14","author":[{"given":"Jackelyn","family":"Murray","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1329-0209","authenticated-orcid":false,"given":"Harrison C.","family":"Bergeron","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Les P.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary Beau","family":"Reener","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2820-5983","authenticated-orcid":false,"given":"David E.","family":"Martin","sequence":"additional","affiliation":[{"name":"TrippBio, Inc., Jacksonville, FL 32256, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred D.","family":"Sancilio","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Florida Atlantic University, Jupiter, FL 33431, 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"},{"name":"TrippBio, Inc., Jacksonville, FL 32256, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1185\/03007995.2010.505126","article-title":"Fatality rates in published reports of RSV hospitalizations among high-risk and otherwise healthy children","volume":"26","author":"Welliver","year":"2010","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1056\/NEJMoa043951","article-title":"Respiratory syncytial virus infection in elderly and high-risk adults","volume":"352","author":"Falsey","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E948","DOI":"10.9778\/cmajo.20200219","article-title":"Health care costs of hospitalization of young children for respiratory syncytial virus infections: A population-based matched cohort study","volume":"9","author":"Thampi","year":"2021","journal-title":"CMAJ Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2147\/CEOR.S60710","article-title":"Respiratory syncytial virus: Current and emerging treatment options","volume":"6","author":"Turner","year":"2014","journal-title":"Clinicoecon. Outcomes Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/cid\/ciy760","article-title":"Oral Versus Aerosolized Ribavirin for the Treatment of Respiratory Syncytial Virus Infections in Hematopoietic Cell Transplant Recipients","volume":"68","author":"Foolad","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"ofy031","DOI":"10.1093\/ofid\/ofy031","article-title":"Palivizumab Prophylaxis for Respiratory Syncytial Virus: Examining the Evidence around Value","volume":"5","author":"Olchanski","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jpeds.2019.06.058","article-title":"Effectiveness of Palivizumab against Respiratory Syncytial Virus: Cohort and Case Series Analysis","volume":"214","author":"Moore","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bawage, S.S., Tiwari, P.M., Pillai, S., Dennis, V.A., and Singh, S.R. (2019). Antibiotic Minocycline Prevents Respiratory Syncytial Virus Infection. Viruses, 11.","DOI":"10.3390\/v11080739"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Bergeron, H.C., and Tripp, R.A. (2021). Immunopathology of RSV: An Updated Review. Viruses, 13.","DOI":"10.3390\/v13122478"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1146\/annurev-biochem-060408-092949","article-title":"Genomic screening with RNAi: Results and challenges","volume":"79","author":"Mohr","year":"2010","journal-title":"Ann. Rev. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1089\/adt.2015.0003.drrr","article-title":"Repurposing Kinase Inhibitors as Antiviral Agents to Control Influenza a Virus Replication","volume":"13","author":"Perwitasari","year":"2015","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_12","first-page":"459","article-title":"Antiviral effects of inhibiting host gene expression","volume":"386","author":"Tripp","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1128\/AAC.01532-12","article-title":"Targeting organic anion transporter 3 with probenecid as a novel anti-influenza a virus strategy","volume":"57","author":"Perwitasari","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1096\/fj.11-193466","article-title":"Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens","volume":"26","author":"Meliopoulos","year":"2012","journal-title":"FASEB J."},{"key":"ref_15","first-page":"193","article-title":"Host gene expression and respiratory syncytial virus infection","volume":"372","author":"Tripp","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e02410-20","DOI":"10.1128\/JVI.02410-20","article-title":"G-Protein-Coupled Receptor and Ion Channel Genes Used by Influenza Virus for Replication","volume":"95","author":"Murray","year":"2021","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1152\/physrev.00025.2013","article-title":"The organic anion transporter (OAT) family: A systems biology perspective","volume":"95","author":"Nigam","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_18","first-page":"F122","article-title":"Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney","volume":"276","author":"Hosoyamada","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"F905","DOI":"10.1152\/ajprenal.00272.2005","article-title":"The human organic anion transporter 3 (OAT3; SLC22A8): Genetic variation and functional genomics","volume":"290","author":"Erdman","year":"2006","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Selo, M.A., Sake, J.A., Ehrhardt, C., and Salomon, J.J. (2020). Organic Cation Transporters in the Lung-Current and Emerging (Patho)Physiological and Pharmacological Concepts. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239168"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3892\/ijmm.2015.2411","article-title":"Repositioning of drugs using open-access data portal DTome: A test case with probenecid (Review)","volume":"37","author":"Ahmed","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cicero, A.F.G., Fogacci, F., Kuwabara, M., and Borghi, C. (2021). Therapeutic Strategies for the Treatment of Chronic Hyperuricemia: An Evidence-Based Update. Medicina, 57.","DOI":"10.3390\/medicina57010058"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/nrmicro2692","article-title":"The dependence of viral RNA replication on co-opted host factors","volume":"10","author":"Nagy","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18085","DOI":"10.1038\/s41598-021-97658-w","article-title":"Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro","volume":"11","author":"Murray","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10710","DOI":"10.1128\/JVI.00986-09","article-title":"Respiratory syncytial virus grown in Vero cells contains a truncated attachment protein that alters its infectivity and dependence on glycosaminoglycans","volume":"83","author":"Kwilas","year":"2009","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6873","DOI":"10.1128\/JVI.76.14.6873-6881.2002","article-title":"Neutralizing anti-F glycoprotein and anti-substance P antibody treatment effectively reduces infection and inflammation associated with respiratory syncytial virus infection","volume":"76","author":"Haynes","year":"2002","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1743-422X-3-63","article-title":"New low-viscosity overlay medium for viral plaque assays","volume":"3","author":"Matrosovich","year":"2006","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9831","DOI":"10.1128\/JVI.77.18.9831-9844.2003","article-title":"Enhanced disease and pulmonary eosinophilia associated with formalin-inactivated respiratory syncytial virus vaccination are linked to G glycoprotein CX3C-CX3CR1 interaction and expression of substance P","volume":"77","author":"Haynes","year":"2003","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.antiviral.2018.04.014","article-title":"Anti-respiratory syncytial virus (RSV) G monoclonal antibodies reduce lung inflammation and viral lung titers when delivered therapeutically in a BALB\/c mouse model","volume":"154","author":"Caidi","year":"2018","journal-title":"Antiviral. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3390\/ph6020124","article-title":"siRNA Genome Screening Approaches to Therapeutic Drug Repositioning","volume":"6","author":"Perwitasari","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/CMR.13.1.1","article-title":"Respiratory syncytial virus genetic and antigenic diversity","volume":"13","author":"Sullender","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1099\/0022-1317-66-10-2111","article-title":"Two distinct subtypes of human respiratory syncytial virus","volume":"66","author":"Mufson","year":"1985","journal-title":"J. Gen. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kim, Y.I., DeVincenzo, J.P., Jones, B.G., Rudraraju, R., Harrison, L., Meyers, R., Cehelsky, J., Alvarez, R., and Hurwitz, J.L. (2014). Respiratory syncytial virus human experimental infection model: Provenance, production, and sequence of low-passaged memphis-37 challenge virus. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113100"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"873","DOI":"10.3389\/fmicb.2019.00873","article-title":"Current Animal Models for Understanding the Pathology Caused by the Respiratory Syncytial Virus","volume":"10","author":"Diaz","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/13543784.2020.1735349","article-title":"Emerging small and large molecule therapeutics for respiratory syncytial virus","volume":"29","author":"Bergeron","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1080\/14712598.2020.1753696","article-title":"Up-to-date role of biologics in the management of respiratory syncytial virus","volume":"20","author":"Tripp","year":"2020","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.3389\/fimmu.2020.01507","article-title":"Current Insights in the Development of Efficacious Vaccines Against RSV","volume":"11","author":"Soto","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eaax2466","DOI":"10.1126\/scitranslmed.aax2466","article-title":"Priorities for developing respiratory syncytial virus vaccines in different target populations","volume":"12","author":"Drysdale","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5654","DOI":"10.1128\/JVI.76.11.5654-5666.2002","article-title":"Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology","volume":"76","author":"Zhang","year":"2002","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1165\/rcmb.2008-0034OC","article-title":"Inhibition of Na+ transport in lung epithelial cells by respiratory syncytial virus infection","volume":"40","author":"Chen","year":"2009","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1016\/j.xphs.2021.02.011","article-title":"Effects of Probenecid on Hepatic and Renal Disposition of Hexadecanedioate, an Endogenous Substrate of Organic Anion Transporting Polypeptide 1B in Rats","volume":"110","author":"Futatsugi","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4939","DOI":"10.1038\/s41598-017-04949-2","article-title":"Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivo Handling of Uremic Toxins and Solutes","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"C761","DOI":"10.1152\/ajpcell.00227.2008","article-title":"Probenecid, a gout remedy, inhibits pannexin 1 channels","volume":"295","author":"Silverman","year":"2008","journal-title":"Am. J. Physiol. Cell Physiol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/5\/912\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:02:07Z","timestamp":1760137327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/5\/912"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["v14050912"],"URL":"https:\/\/doi.org\/10.3390\/v14050912","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-1280404\/v1","asserted-by":"object"}]},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,27]]}}}