Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Antiviral research, 2024-07, Vol.227, p.105907, Article 105907

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •JNJ-7184 has an average in vitro EC50 of 13/72 nM on RSV-A/B strains.•JNJ-7184 targets the connector domain of the L polymerase.•It blocks early elongation of vRNA products and partly 1st dinucleotide formation.•Methyltransferase activity is barely impacted.•It is active in primary air-liquid interface cultures and the neonatal lamb model.