{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:15:31Z","timestamp":1787030131392,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Georgia Research Alliance"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Avian influenza (AI) viruses cause infection in birds and humans. Several H5N1 and H7N9 variants are highly pathogenic avian influenza (HPAI) viruses. H5N1 is a highly infectious bird virus infecting primarily poultry, but unlike other AIs, H5N1 also infects mammals and transmits to humans with a case fatality rate above 40%. Similarly, H7N9 can infect humans, with a case fatality rate of over 40%. Since 1996, there have been several HPAI outbreaks affecting humans, emphasizing the need for safe and effective antivirals. We show that probenecid potently inhibits H5N1 and H7N9 replication in prophylactically or therapeutically treated A549 cells and normal human broncho-epithelial (NHBE) cells, and H5N1 replication in VeroE6 cells and mice.<\/jats:p>","DOI":"10.3390\/v16010152","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T11:04:57Z","timestamp":1705662297000},"page":"152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Probenecid Inhibits Influenza A(H5N1) and A(H7N9) Viruses In Vitro and in Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Jackelyn","family":"Murray","sequence":"first","affiliation":[{"name":"Animal Health Research Center, Department of Infectious Diseases, College of Veterinary Medicine Athens, University of Georgia, Athens, GA 30605, 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":"Sarah","family":"Hosking","sequence":"additional","affiliation":[{"name":"Animal Health Research Center, Department of Infectious Diseases, College of Veterinary Medicine Athens, University of Georgia, Athens, GA 30605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-2484","authenticated-orcid":false,"given":"Nichole","family":"Orr-Burks","sequence":"additional","affiliation":[{"name":"Animal Health Research Center, Department of Infectious Diseases, College of Veterinary Medicine Athens, University of Georgia, Athens, GA 30605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Animal Health Research Center, Department of Infectious Diseases, College of Veterinary Medicine Athens, University of Georgia, Athens, GA 30605, 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":"Animal Health Research Center, Department of Infectious Diseases, College of Veterinary Medicine Athens, University of Georgia, Athens, GA 30605, USA"},{"name":"TrippBio, Inc., Jacksonville, FL 32256, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Murray, J., Martin, D.E., Sancilio, F.D., and Tripp, R.A. (2023). Antiviral Activity of Probenecid and Oseltamivir on Influenza Virus Replication. Viruses, 15.","DOI":"10.3390\/v15122366"},{"key":"ref_2","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_3","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_4","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_5","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_6","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_7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1179\/2047773213Y.0000000103","article-title":"Global alert to avian influenza virus infection: From H5N1 to H7N9","volume":"107","author":"Poovorawan","year":"2013","journal-title":"Pathog. Glob. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/rmv.1846","article-title":"Molecular pathogenesis of H5 highly pathogenic avian influenza: The role of the haemagglutinin cleavage site motif","volume":"25","author":"Luczo","year":"2015","journal-title":"Rev. Med. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.2353\/ajpath.2008.070791","article-title":"Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans","volume":"172","author":"Korteweg","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00604-17","DOI":"10.1128\/AEM.00604-17","article-title":"Survival of Highly Pathogenic Avian Influenza H5N1 Virus in Tissues Derived from Experimentally Infected Chickens","volume":"83","author":"Yamamoto","year":"2017","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJMoa1304459","article-title":"Human infection with a novel avian-origin influenza A (H7N9) virus","volume":"368","author":"Gao","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/nature12372","article-title":"Receptor binding by an H7N9 influenza virus from humans","volume":"499","author":"Xiong","year":"2013","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1126\/science.1242917","article-title":"Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses","volume":"342","author":"Shi","year":"2013","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cai, M., Zhong, R., Qin, C., Yu, Z., Wen, X., Xian, J., Chen, Y., Cai, Y., Yi, H., and Gong, L. (2020). The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses. Viruses, 12.","DOI":"10.3390\/v12010052"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1093\/cid\/civ345","article-title":"Differences in the Epidemiology of Human Cases of Avian Influenza A(H7N9) and A(H5N1) Viruses Infection","volume":"61","author":"Qin","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.vaccine.2018.11.069","article-title":"Safety and immunogenicity of influenza A(H5N1) vaccine stored up to twelve years in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS)","volume":"37","author":"Oshansky","year":"2019","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Levine, M.Z., Holiday, C., Bai, Y., Zhong, W., Liu, F., Jefferson, S., Gross, F.L., Tzeng, W.P., Fries, L., and Smith, G. (2022). Influenza A(H7N9) Pandemic Preparedness: Assessment of the Breadth of Heterologous Antibody Responses to Emerging Viruses from Multiple Pre-Pandemic Vaccines and Population Immunity. Vaccines, 10.","DOI":"10.3390\/vaccines10111856"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dey, P., Ahuja, A., Panwar, J., Choudhary, P., Rani, S., Kaur, M., Sharma, A., Kaur, J., Yadav, A.K., and Sood, V. (2023). Immune Control of Avian Influenza Virus Infection and Its Vaccine Development. Vaccines, 11.","DOI":"10.3390\/vaccines11030593"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e02154-20","DOI":"10.1128\/JVI.02154-20","article-title":"A Replication-Defective Influenza Virus Harboring H5 and H7 Hemagglutinins Provides Protection against H5N1 and H7N9 Infection in Mice","volume":"95","author":"Tian","year":"2021","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1056\/NEJMoa1305584","article-title":"Clinical findings in 111 cases of influenza A (H7N9) virus infection","volume":"368","author":"Gao","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1016\/S0140-6736(13)60903-4","article-title":"Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: Clinical analysis and characterisation of viral genome","volume":"381","author":"Chen","year":"2013","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12418","DOI":"10.1128\/JVI.01067-07","article-title":"Neuraminidase inhibitor-resistant recombinant A\/Vietnam\/1203\/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo","volume":"81","author":"Yen","year":"2007","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ilyushina, N.A., Seiler, J.P., Rehg, J.E., Webster, R.G., and Govorkova, E.A. (2010). Effect of neuraminidase inhibitor-resistant mutations on pathogenicity of clade 2.2 A\/Turkey\/15\/06 (H5N1) influenza virus in ferrets. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000933"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105499","DOI":"10.1016\/j.antiviral.2022.105499","article-title":"Influenza antivirals and their role in pandemic preparedness","volume":"210","author":"Jones","year":"2023","journal-title":"Antivir. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41591-021-01282-0","article-title":"Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases","volume":"27","author":"Meganck","year":"2021","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00168-19","DOI":"10.1128\/CMR.00168-19","article-title":"Host-Directed Antiviral Therapy","volume":"33","author":"Kumar","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1093\/infdis\/jiab305","article-title":"Report of the National Institutes of Health SARS-CoV-2 Antiviral Therapeutics Summit","volume":"224","author":"Hall","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_29","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_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":"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_32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/978-1-60327-295-7_4","article-title":"Therapeutic applications of RNAi for silencing virus replication","volume":"555","author":"Tripp","year":"2009","journal-title":"Methods Mol Biol"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104","DOI":"10.4062\/biomolther.2019.047","article-title":"Inhibitory Effect of Probenecid on Osteoclast Formation via JNK, ROS and COX-2","volume":"28","author":"Cheng","year":"2020","journal-title":"Biomol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Veto, B., Bojcsuk, D., Bacquet, C., Kiss, J., Sipeki, S., Martin, L., Buday, L., Balint, B.L., and Aranyi, T. (2017). The transcriptional activity of hepatocyte nuclear factor 4 alpha is inhibited via phosphorylation by ERK1\/2. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172020"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"F1819-26","DOI":"10.1152\/ajprenal.00017.2007","article-title":"Hepatocyte nuclear factor-4alpha regulates the human organic anion transporter 1 gene in the kidney","volume":"292","author":"Ogasawara","year":"2007","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Xue, J., Chambers, B.S., Hensley, S.E., and Lopez, C.B. (2016). Propagation and Characterization of Influenza Virus Stocks That Lack High Levels of Defective Viral Genomes and Hemagglutinin Mutations. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00326"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A Simple Method of Estimating Fifty per cent ENDPOINTS12","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12757","DOI":"10.1038\/s41598-022-16605-5","article-title":"Sialylated and sulfated N-Glycans in MDCK and engineered MDCK cells for influenza virus studies","volume":"12","author":"Jia","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1128\/JVI.02790-15","article-title":"Identification of Stabilizing Mutations in an H5 Hemagglutinin Influenza Virus Protein","volume":"90","author":"Hanson","year":"2015","journal-title":"J. Virol."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","unstructured":"Matheson, N.J., Harnden, A.R., Perera, R., Sheikh, A., and Symmonds-Abrahams, M. (2007). Neuraminidase inhibitors for preventing and treating influenza in children. Cochrane Database Syst. Rev., CD002744.","DOI":"10.1002\/14651858.CD002744.pub2"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"ii5","DOI":"10.1093\/jac\/dkq015","article-title":"Pharmacokinetics of oseltamivir: An oral antiviral for the treatment and prophylaxis of influenza in diverse populations","volume":"65","author":"Davies","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1750-2659.2011.00235.x","article-title":"Oseltamivir treatment of mice before or after mild influenza infection reduced cellular and cytokine inflammation in the lung","volume":"5","author":"Wong","year":"2011","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3389\/fimmu.2016.00060","article-title":"Avian Influenza Viruses, Inflammation, and CD8(+) T Cell Immunity","volume":"7","author":"Wang","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10942","DOI":"10.1038\/srep10942","article-title":"The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes","volume":"5","author":"Guo","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1073\/pnas.1321748111","article-title":"Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection","volume":"111","author":"Wang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/1465-9921-6-135","article-title":"Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells","volume":"6","author":"Chan","year":"2005","journal-title":"Respir. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4655","DOI":"10.1128\/JVI.03095-14","article-title":"A(H7N9) virus results in early induction of proinflammatory cytokine responses in both human lung epithelial and endothelial cells and shows increased human adaptation compared with avian H5N1 virus","volume":"89","author":"Zeng","year":"2015","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12479","DOI":"10.1073\/pnas.0705289104","article-title":"Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection","volume":"104","author":"Salomon","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7625","DOI":"10.1038\/s41598-017-07384-5","article-title":"The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome","volume":"7","author":"Ren","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/cmi.2015.74","article-title":"The cytokine storm of severe influenza and development of immunomodulatory therapy","volume":"13","author":"Liu","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"300060519845488","DOI":"10.1177\/0300060519845488","article-title":"Virus-induced pathogenesis, vaccine development, and diagnosis of novel H7N9 avian influenza A virus in humans: A systemic literature review","volume":"48","author":"Wang","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/JS9.0000000000000157","article-title":"Human death due to H5N1 amid the COVID-19 pandemic and Mpox outbreak: A call for action","volume":"109","author":"Sah","year":"2023","journal-title":"Int. J. Surg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.3201\/eid2308.170640","article-title":"Preliminary Epidemiology of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017","volume":"23","author":"Zhou","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Balgi, A.D., Wang, J., Cheng, D.Y., Ma, C., Pfeifer, T.A., Shimizu, Y., Anderson, H.J., Pinto, L.H., Lamb, R.A., and DeGrado, W.F. (2013). Inhibitors of the influenza A virus M2 proton channel discovered using a high-throughput yeast growth restoration assay. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055271"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Smyk, J.M., Szydlowska, N., Szulc, W., and Majewska, A. (2022). Evolution of Influenza Viruses-Drug Resistance, Treatment Options, and Prospects. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012244"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1016\/j.jmb.2018.06.024","article-title":"Virus-Receptor Interactions: The Key to Cellular Invasion","volume":"430","author":"Maginnis","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5419","DOI":"10.1128\/JVI.03513-14","article-title":"Neuraminidase Mutations Conferring Resistance to Oseltamivir in Influenza A(H7N9) Viruses","volume":"89","author":"Marjuki","year":"2015","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41421-023-00571-x","article-title":"Potential cross-species transmission of highly pathogenic avian influenza H5 subtype (HPAI H5) viruses to humans calls for the development of H5-specific and universal influenza vaccines","volume":"9","author":"Huang","year":"2023","journal-title":"Cell. Discov."},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"13775","DOI":"10.1128\/JVI.01509-13","article-title":"Targeting cell division cycle 25 homolog B to regulate influenza virus replication","volume":"87","author":"Perwitasari","year":"2013","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Bakre, A., Andersen, L.E., Meliopoulos, V., Coleman, K., Yan, X., Brooks, P., Crabtree, J., Tompkins, S.M., and Tripp, R.A. (2013). Identification of Host Kinase Genes Required for Influenza Virus Replication and the Regulatory Role of MicroRNAs. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066796"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1080\/00498254.2016.1187777","article-title":"Probenecid, an organic anion transporter 1 and 3 inhibitor, increases plasma and brain exposure of N-acetylcysteine","volume":"47","author":"Hagos","year":"2017","journal-title":"Xenobiotica"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1001\/archinte.1955.00250070099012","article-title":"Probenecid (benemid); its uses and side-effects in 2,502 patients","volume":"95","author":"Boger","year":"1955","journal-title":"AMA Arch. Intern. Med."},{"key":"ref_65","first-page":"691","article-title":"The role of the c-Jun N-terminal Kinase signaling pathway in skin cancer","volume":"2","author":"Zhang","year":"2012","journal-title":"Am. J. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Chen, J., Ye, C., Wan, C., Li, G., Peng, L., Peng, Y., and Fang, R. (2021). The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179640"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13700","DOI":"10.1128\/JVI.01683-07","article-title":"ERK- and JNK-dependent signaling pathways contribute to Bombyx mori nucleopolyhedrovirus infection","volume":"81","author":"Katsuma","year":"2007","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1194\/jlr.M088880","article-title":"Repression of hepatocyte nuclear factor 4 alpha by AP-1 underlies dyslipidemia associated with retinoic acid","volume":"60","author":"Won","year":"2019","journal-title":"J. Lipid. Res."},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"e0194","DOI":"10.1097\/MD.0000000000010194","article-title":"Comparison of patients with avian influenza A (H7N9) and influenza A (H1N1) complicated by acute respiratory distress syndrome","volume":"97","author":"Li","year":"2018","journal-title":"Medicine"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"12982","DOI":"10.1128\/JVI.01571-14","article-title":"Human H7N9 and H5N1 influenza viruses differ in induction of cytokines and tissue tropism","volume":"88","author":"Meliopoulos","year":"2014","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"L121","DOI":"10.1152\/ajplung.00146.2020","article-title":"Consideration of Pannexin 1 channels in COVID-19 pathology and treatment","volume":"319","author":"Swayne","year":"2020","journal-title":"Am. J. Physiol. Lung. Cell. Mol. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.1111\/bph.14787","article-title":"Repurposing drugs targeting the P2 \u00d7 7 receptor to limit hyperinflammation and disease during influenza virus infection","volume":"176","author":"Rosli","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Sinha, S., Cheng, K., Schaffer, A.A., Aldape, K., Schiff, E., and Ruppin, E. (2020). In vitro and in vivo identification of clinically approved drugs that modify ACE2 expression. Mol. Syst. Biol., 16.","DOI":"10.15252\/msb.20209628"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1073\/pnas.94.12.6358","article-title":"Mast cell tumor necrosis factor alpha production is regulated by MEK kinases","volume":"94","author":"Ishizuka","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S1074-7613(00)80038-2","article-title":"Impaired on\/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: Implications for joint and gut-associated immunopathologies","volume":"10","author":"Kontoyiannis","year":"1999","journal-title":"Immunity"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6274","DOI":"10.1128\/MCB.17.11.6274","article-title":"Jun N-terminal kinase\/stress-activated protein kinase (JNK\/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: Glucocorticoids inhibit TNF-alpha translation by blocking JNK\/SAPK","volume":"17","author":"Swantek","year":"1997","journal-title":"Mol. Cell. Biol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/1\/152\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:46:11Z","timestamp":1760103971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/1\/152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,19]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["v16010152"],"URL":"https:\/\/doi.org\/10.3390\/v16010152","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,19]]}}}