{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:24:04Z","timestamp":1791415444735,"version":"4.3.3"},"reference-count":64,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"21","funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI171403 project 3"],"award-info":[{"award-number":["AI171403 project 3"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI171403 scientific core B"],"award-info":[{"award-number":["AI171403 scientific core B"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI171403 scientific core C"],"award-info":[{"award-number":["AI171403 scientific core C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI171403 scientific core D"],"award-info":[{"award-number":["AI171403 scientific core D"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI171403 scientific core F"],"award-info":[{"award-number":["AI171403 scientific core F"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI071002"],"award-info":[{"award-number":["AI071002"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI171403 core A"],"award-info":[{"award-number":["AI171403 core A"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI171403 core A"],"award-info":[{"award-number":["AI171403 core A"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI171403 scientific core C"],"award-info":[{"award-number":["AI171403 scientific core C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,5,22]]},"abstract":"<jats:p>Orthoparamyxoviruses, such as human parainfluenza virus type 3 (HPIV3) and measles virus (MeV), are a major health threat. We discovered an orally efficacious broad-spectrum inhibitor of orthoparamyxovirus polymerases. However, here, we found that tolerability in higher mammals was limited. We report the development of the clinical candidate analog GHP-88310 (EIDD-3608), which combines improved oral efficacy with favorable tolerability in nonrodents (ferrets and dogs). GHP-88310 was active against HPIV3, Sendai virus (SeV), MeV, and related canine distemper virus (CDV). In 7-day tolerability studies, daily doses of 2000 mg\/kg were well tolerated. Pharmacokinetic analysis revealed altered plasma exposure of GHP-88310 compared to the original hit. In HPIV3-infected cotton rats, GHP-88310 lowered the respiratory tract viral load. Dosing of ferrets infected with CDV, causing lethal measles-like disease, resulted in complete survival, reduction of viremia and shed viral load, and alleviated lymphocytopenia. Once-daily GHP-88310 was efficacious in the CDV-ferret and HPIV3-cotton rat models. The compound was sterilizing against HPIV3 at physiological concentrations in human airway epithelium organoids.<\/jats:p>","DOI":"10.1126\/sciadv.aef1594","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T17:58:41Z","timestamp":1779472721000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Developmental candidate GHP-88310\/EIDD-3608 with high tolerability and oral efficacy in measles and respiratory paramyxovirus models"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6845-2746","authenticated-orcid":true,"given":"Carolin M.","family":"Lieber","sequence":"first","affiliation":[{"name":"Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2507-6944","authenticated-orcid":true,"given":"Josef D.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mugunthan","family":"Govindarajan","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9379-0416","authenticated-orcid":true,"given":"Jeong-Joong","family":"Yoon","sequence":"additional","affiliation":[{"name":"Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7022-1410","authenticated-orcid":true,"given":"Zachary M.","family":"Sticher","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7223-7857","authenticated-orcid":true,"given":"Claire E.","family":"Ruckel","sequence":"additional","affiliation":[{"name":"Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7875-9258","authenticated-orcid":true,"given":"Alexander I.","family":"Leach","sequence":"additional","affiliation":[{"name":"Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5299-4893","authenticated-orcid":true,"given":"Lauren A.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4242-9978","authenticated-orcid":true,"given":"Dariia","family":"Vyshenska","sequence":"additional","affiliation":[{"name":"Virology Division, Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5929-3568","authenticated-orcid":true,"given":"Amalia A.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8491-3824","authenticated-orcid":true,"given":"Meghan K.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1962-7578","authenticated-orcid":true,"given":"Rebecca E.","family":"Krueger","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Cox","sequence":"additional","affiliation":[{"name":"Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9803-8095","authenticated-orcid":true,"given":"George R.","family":"Painter","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-0527","authenticated-orcid":true,"given":"Alexander L.","family":"Greninger","sequence":"additional","affiliation":[{"name":"Virology Division, Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Natchus","sequence":"additional","affiliation":[{"name":"Emory Institute for Drug Development, Emory University, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2034-2107","authenticated-orcid":true,"given":"Richard K.","family":"Plemper","sequence":"additional","affiliation":[{"name":"Center for Translational Antiviral Research, Georgia State University Institute for Biomedical Sciences, Atlanta, GA 30303, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"R. K. Plemper R. A. Lamb in Fields Virology D. M. Knipe P. M. Howley S. Whelan Eds. (Wolters Kluwer\/Lippincott Williams and Wilkins 2020) vol. 1 chap. 33 pp. 504\u2013558."},{"key":"e_1_3_2_3_2","unstructured":"B. Lee C. C. Broder L. Wang in Fields Virology D. M. Knipe P. M. Howley S. Whelan Eds. (Wolters Kluwer\/Lippincott Williams and Wilkins 2020) vol. 1 chap. 34 pp. 559\u2013595."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)11096-0"},{"key":"e_1_3_2_5_2","first-page":"E199","article-title":"Lancet retracts 12-year-old article linking autism to MMR vaccines","volume":"182","author":"Eggertson L.","year":"2010","unstructured":"L. Eggertson, Lancet retracts 12-year-old article linking autism to MMR vaccines. Curr. Opin. Virol. 182, E199\u2013E200 (2010).","journal-title":"Curr. Opin. Virol."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2106441"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2504516"},{"key":"e_1_3_2_8_2","unstructured":"CDC Measles Cases and Outbreaks (2025); https:\/\/www.cdc.gov\/measles\/data-research\/index.html."},{"key":"e_1_3_2_9_2","unstructured":"World Health Organization Measles in the Region of the Americas (2025); https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/2025-DON565."},{"key":"e_1_3_2_10_2","unstructured":"Goverment of Canada Measles and rubella weekly monitoring report (2025); https:\/\/health-infobase.canada.ca\/measles-rubella\/."},{"key":"e_1_3_2_11_2","unstructured":"National Medial Association NMA Statement on Measles Outbreak\u2014Children\u2019s Lives in Danger in West Texas (2025); https:\/\/nmanet.org\/press-release\/nma-statement-on-measles-outbreak-childrens-lives-in-danger-in-west-texas\/."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2020.02.007"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.944436"},{"key":"e_1_3_2_14_2","unstructured":"S. S. Chen Measles Treatment and Management (2025); https:\/\/emedicine.medscape.com\/article\/966220-treatment?form=fpf."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1586\/ecp.09.40"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13643-024-02698-8"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15102431"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195904092601501"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1986.02140150036029"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-12-060343"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.3.573"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.1.1.1424"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piu047"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0752-7"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00806-24"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45418-5"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00800-24"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2006.03.009"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.49"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(01)00255-6"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.06.017"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58985-y"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1177\/2211068214561025"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobme.2025.100588"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2008.02.023"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03831-21"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.2.1113-1124.2005"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912955107"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41684-024-01473-5"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53560"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2.6.875"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(93)90252-R"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfae056"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S526727"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1177\/20417314241232502"},{"key":"e_1_3_2_47_2","doi-asserted-by":"crossref","unstructured":"J. H. Lee J. C. Le Cher E. Parigoris N. Shinagawa J. Sentosa C. Manfredi S. L. Goh R. De S. Tao K. Zandi F. Amblard E. J. Sorscher J. R. Spence R. Tirouvanziam R. F. Schinazi S. Takayama Development of robust antiviral assays using relevant apical-out human airway organoids. bioRxiv [Preprint] (2024); https:\/\/doi.org\/10.1101\/2024.01.02.573939.","DOI":"10.1101\/2024.01.02.573939"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1532144"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax5866"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21461"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.11.6900-6908.2005"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.04.025"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.8.3802-3810.2001"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01241-7"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.8.6559-6565.1999"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj5508"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012299115260"},{"key":"e_1_3_2_58_2","unstructured":"W. B. Thomas The Neurologic Examination of Animals (2023); https:\/\/www.merckvetmanual.com\/nervous-system\/the-neurologic-examination\/the-neurologic-examination-of-animals."},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-77872-y"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01881-16"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3820"},{"key":"e_1_3_2_63_2","doi-asserted-by":"crossref","unstructured":"M. J. Lin R. C. Shean N. Makhsous A. L. Greninger LAVA: A streamlined visualization tool for longitudinal analysis of viral alleles. bioRxiv [Preprint] (2019); https:\/\/doi.org\/10.1101\/2019.12.17.879320.","DOI":"10.1101\/2019.12.17.879320"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009371"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo2236"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aef1594","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T17:59:45Z","timestamp":1779472785000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aef1594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":64,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2026,5,22]]}},"alternative-id":["10.1126\/sciadv.aef1594"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aef1594","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]},"assertion":[{"value":"2026-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaef1594"}}