Brecht Bonneux , Afzaal Shareef , Sergey Tcherniuk , Brandon Anson , Suzanne de Bruyn , Nick Verheyen , Kim Thys , Nádia Conceição-Neto , Marcia Van Ginderen , Leen Kwanten , Nina Ysebaert , Luc Vranckx , Elien Peeters , Ellen Lanckacker , Jack M. Gallup , Panchan Sitthicharoenchai , Sarhad Alnajjar , Mark R. Ackermann , Suraj Adhikary , Anusarka Bhaumik , Florence Herschke
{"title":"JNJ-7184 是一种针对病毒聚合酶接头结构域的呼吸道合胞病毒抑制剂。","authors":"Brecht Bonneux , Afzaal Shareef , Sergey Tcherniuk , Brandon Anson , Suzanne de Bruyn , Nick Verheyen , Kim Thys , Nádia Conceição-Neto , Marcia Van Ginderen , Leen Kwanten , Nina Ysebaert , Luc Vranckx , Elien Peeters , Ellen Lanckacker , Jack M. Gallup , Panchan Sitthicharoenchai , Sarhad Alnajjar , Mark R. Ackermann , Suraj Adhikary , Anusarka Bhaumik , Florence Herschke","doi":"10.1016/j.antiviral.2024.105907","DOIUrl":null,"url":null,"abstract":"<div><p>Respiratory syncytial virus (RSV) can cause pulmonary complications in infants, elderly and immunocompromised patients. While two vaccines and two prophylactic monoclonal antibodies are now available, treatment options are still needed. JNJ-7184 is a non-nucleoside inhibitor of the RSV-Large (L) polymerase, displaying potent inhibition of both RSV-A and -B strains. Resistance selection and hydrogen-deuterium exchange experiments suggest JNJ-7184 binds RSV-L in the connector domain. JNJ-7184 prevents RSV replication and transcription by inhibiting initiation or early elongation. JNJ-7184 is effective in air-liquid interface cultures and therapeutically in neonatal lambs, acting to drastically reverse the appearance of lung pathology.</p></div>","PeriodicalId":8259,"journal":{"name":"Antiviral research","volume":"227 ","pages":"Article 105907"},"PeriodicalIF":4.3000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"JNJ-7184, a respiratory syncytial virus inhibitor targeting the connector domain of the viral polymerase\",\"authors\":\"Brecht Bonneux , Afzaal Shareef , Sergey Tcherniuk , Brandon Anson , Suzanne de Bruyn , Nick Verheyen , Kim Thys , Nádia Conceição-Neto , Marcia Van Ginderen , Leen Kwanten , Nina Ysebaert , Luc Vranckx , Elien Peeters , Ellen Lanckacker , Jack M. Gallup , Panchan Sitthicharoenchai , Sarhad Alnajjar , Mark R. Ackermann , Suraj Adhikary , Anusarka Bhaumik , Florence Herschke\",\"doi\":\"10.1016/j.antiviral.2024.105907\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Respiratory syncytial virus (RSV) can cause pulmonary complications in infants, elderly and immunocompromised patients. While two vaccines and two prophylactic monoclonal antibodies are now available, treatment options are still needed. JNJ-7184 is a non-nucleoside inhibitor of the RSV-Large (L) polymerase, displaying potent inhibition of both RSV-A and -B strains. Resistance selection and hydrogen-deuterium exchange experiments suggest JNJ-7184 binds RSV-L in the connector domain. JNJ-7184 prevents RSV replication and transcription by inhibiting initiation or early elongation. JNJ-7184 is effective in air-liquid interface cultures and therapeutically in neonatal lambs, acting to drastically reverse the appearance of lung pathology.</p></div>\",\"PeriodicalId\":8259,\"journal\":{\"name\":\"Antiviral research\",\"volume\":\"227 \",\"pages\":\"Article 105907\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antiviral research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0166354224001165\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antiviral research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0166354224001165","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
JNJ-7184, a respiratory syncytial virus inhibitor targeting the connector domain of the viral polymerase
Respiratory syncytial virus (RSV) can cause pulmonary complications in infants, elderly and immunocompromised patients. While two vaccines and two prophylactic monoclonal antibodies are now available, treatment options are still needed. JNJ-7184 is a non-nucleoside inhibitor of the RSV-Large (L) polymerase, displaying potent inhibition of both RSV-A and -B strains. Resistance selection and hydrogen-deuterium exchange experiments suggest JNJ-7184 binds RSV-L in the connector domain. JNJ-7184 prevents RSV replication and transcription by inhibiting initiation or early elongation. JNJ-7184 is effective in air-liquid interface cultures and therapeutically in neonatal lambs, acting to drastically reverse the appearance of lung pathology.
期刊介绍：
Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.
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