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

Bonneux, Brecht; Shareef, Afzaal; Tcherniuk, Sergey; Anson, Brandon; de Bruyn, Suzanne; Verheyen, Nick; Thys, Kim; Conceição-Neto, Nádia; Van Ginderen, Marcia; Kwanten, Leen; Ysebaert, Nina; Vranckx, Luc; Peeters, Elien; Lanckacker, Ellen; Gallup, Jack M.; Sitthicharoenchai, Panchan; Alnajjar, Sarhad; Ackermann, Mark R.; Adhikary, Suraj; Bhaumik, Anusarka; Patrick, Aaron; Fung, Amy; Sutto-Ortiz, Priscila; Decroly, Etienne; Mason, Stephen W.; Lançois, David; Deval, Jerome; Jin, Zhinan; Eléouët, Jean-François; Fearns, Rachel; Koul, Anil; Roymans, Dirk; Rigaux, Peter; Herschke, Florence

doi:10.1016/j.antiviral.2024.105907

Cited by 2 publications

(2 citation statements)

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“…131 One year later, researchers at Janssen, in collaboration with various universities, reported the identification of the pyrazolopyrimidine analogue 50 (JNJ-7184, Figure 16) as an allosteric NNI of RSV L polymerase. 132 This identification was made following a HTS of an undisclosed library tested on HeLa cells infected with the RSV A2 reporter strain. Compound 50 exhibited an EC 50 of 14 nM, coupled with a CC 50 of 52 μM, and retained low nM EC 50 values against a wide panel of RSV clinical isolates.…”

Section: ■ Inhibitiors Of the Replication Complexmentioning

confidence: 99%

“…Notably, the binding pocket of 49 differed from that of 31 , which retained its anti-RSV activity even against the RSV strain carrying the C1388G mutation . One year later, researchers at Janssen, in collaboration with various universities, reported the identification of the pyrazolopyrimidine analogue 50 (JNJ-7184, Figure ) as an allosteric NNI of RSV L polymerase . This identification was made following a HTS of an undisclosed library tested on HeLa cells infected with the RSV A2 reporter strain.…”

Section: Inhibitiors Of the Replication Complexmentioning

confidence: 99%

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Recent Progress toward the Discovery of Small Molecules as Novel Anti-Respiratory Syncytial Virus Agents

Felicetti,

Sarnari,

Gaito

et al. 2024

J. Med. Chem.

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Respiratory syncytial virus (RSV) stands as the foremost cause of infant hospitalization globally, ranking second only to malaria in terms of infant mortality. Although three vaccines have recently been approved for the prophylaxis of adults aged 60 and above, and pregnant women, there is currently no effective antiviral drug for treating RSV infections. The only preventive measure for infants at high risk of severe RSV disease is passive immunization through monoclonal antibodies. This Perspective offers an overview of the latest advancements in RSV drug discovery of small molecule antivirals, with particular focus on the promising findings from agents targeting the fusion and polymerase proteins. A comprehensive reflection on the current state of RSV research is also given, drawing inspiration from the lessons gleaned from HCV and HIV, while also considering the impact of the recent approval of the three vaccines.

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Section: ■ Inhibitiors Of the Replication Complexmentioning

confidence: 99%

Section: Inhibitiors Of the Replication Complexmentioning

confidence: 99%