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

  • Antiviral Res. 2024 Jul:227:105907. doi: 10.1016/j.antiviral.2024.105907.
Brecht Bonneux  1 ,  Afzaal Shareef  2 ,  Sergey Tcherniuk  3 ,  Brandon Anson  4 ,  Suzanne de Bruyn  5 ,  Nick Verheyen  5 ,  Kim Thys  5 ,  Nádia Conceição-Neto  5 ,  Marcia Van Ginderen  5 ,  Leen Kwanten  5 ,  Nina Ysebaert  5 ,  Luc Vranckx  5 ,  Elien Peeters  5 ,  Ellen Lanckacker  5 ,  Jack M Gallup  6 ,  Panchan Sitthicharoenchai  6 ,  Sarhad Alnajjar  6 ,  Mark R Ackermann  6 ,  Suraj Adhikary  4 ,  Anusarka Bhaumik  4 ,  Aaron Patrick  4 ,  Amy Fung  4 ,  Priscila Sutto-Ortiz  7 ,  Etienne Decroly  7 ,  Stephen W Mason  4 ,  David Lançois  8 ,  Jerome Deval  4 ,  Zhinan Jin  4 ,  Jean-François Eléouët  3 ,  Rachel Fearns  2 ,  Anil Koul  9 ,  Dirk Roymans  5 ,  Peter Rigaux  5 ,  Florence Herschke  10
Affiliations
  • 1. Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsbaan 1, 2610 Wilrijk, Belgium; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
  • 2. Department of Virology, Immunology & Microbiology, National Emerging Infectious Diseases Laboratories, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.
  • 3. Unité de Virologie et Immunologie Moléculaires (VIM, UMR892), INRAE, Université Paris-Saclay, 78352 Jouy-en-Josas, France.
  • 4. Janssen Research & Development LLC, Spring House (PA 19477) And Brisbane (CA 94005), USA.
  • 5. Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
  • 6. Iowa State University, Ames, IA 50011, USA.
  • 7. AFMB, Aix-Marseille University, CNRS UMR 7257, 163 Avenue de Luminy, Marseille, France.
  • 8. Janssen France, 27106 Val de Reuil, France.
  • 9. Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: [email protected].
  • 10. Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: [email protected].
PMID: 38772503 DOI: 10.1016/j.antiviral.2024.105907
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.

Keywords
Connector domain; Direct anti-viral; Non-nucleos(t)ide inhibitor; Respiratory syncytial virus; Viral polymerase.
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