JNJ-7184, a respiratory syncytial virus inhibitor targeting the connector domain of the viral polymerase

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY Antiviral research Pub Date : 2024-05-19 DOI:10.1016/j.antiviral.2024.105907

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

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引用次数: 0

Abstract

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.

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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。

呼吸道合胞病毒（RSV）可导致婴儿、老年人和免疫力低下患者出现肺部并发症。虽然目前已有两种疫苗和两种预防性单克隆抗体，但仍需要治疗方案。JNJ-7184 是 RSV-Large (L) 聚合酶的非核苷抑制剂，对 RSV-A 和 -B 株都有很强的抑制作用。抗药性选择和氢氘交换实验表明，JNJ-7184 能在连接域结合 RSV-L。JNJ-7184 通过抑制起始或早期延伸来阻止 RSV 复制和转录。JNJ-7184 在气液界面培养和新生羔羊治疗中都很有效，能显著逆转肺部病变的出现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

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.