作者
Olivia Goethals, Suzanne JF Kaptein, Bart Kesteleyn, Jean-François Bonfanti, Liesbeth Van Wesenbeeck, Dorothée Bardiot, Ernst J Verschoor, Babs E Verstrepen, Zahra Fagrouch, J Robert Putnak, Dominik Kiemel, Oliver Ackaert, Roel Straetemans, Sophie Lachau-Durand, Peggy Geluykens, Marjolein Crabbe, Kim Thys, Bart Stoops, Oliver Lenz, Lotke Tambuyzer, Sandra De Meyer, Kai Dallmeier, Michael K McCracken, Gregory D Gromowski, Wiriya Rutvisuttinunt, Richard G Jarman, Nicos Karasavvas, Franck Touret, Gilles Querat, Xavier de Lamballerie, Laurent Chatel-Chaix, Gregg N Milligan, David WC Beasley, Nigel Bourne, Alan DT Barrett, Arnaud Marchand, Tim HM Jonckers, Pierre Raboisson, Kenny Simmen, Patrick Chaltin, Ralf Bartenschlager, Willy M Bogers, Johan Neyts, Marnix Van Loock
发表日期
2023/3/23
期刊
Nature
卷号
615
期号
7953
页码范围
678-686
出版商
Nature Publishing Group UK
简介
Dengue is a major health threat and the number of symptomatic infections caused by the four dengue serotypes is estimated to be 96 million with annually around 10,000 deaths. However, no antiviral drugs are available for the treatment or prophylaxis of dengue. We recently described the interaction between non-structural proteins NS3 and NS4B as a promising target for the development of pan-serotype dengue virus (DENV) inhibitors. Here we present JNJ-1802—a highly potent DENV inhibitor that blocks the NS3–NS4B interaction within the viral replication complex. JNJ-1802 exerts picomolar to low nanomolar in vitro antiviral activity, a high barrier to resistance and potent in vivo efficacy in mice against infection with any of the four DENV serotypes. Finally, we demonstrate that the small-molecule inhibitor JNJ-1802 is highly effective against viral infection with DENV-1 or DENV-2 in non-human primates. JNJ …
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O Goethals, SJF Kaptein, B Kesteleyn, JF Bonfanti… - Nature, 2023