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

Autor: Bonneux B; Laboratory for Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsbaan 1, 2610 Wilrijk, Belgium; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Shareef A; Department of Virology, Immunology & Microbiology, National Emerging Infectious Diseases Laboratories, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Tcherniuk S; Unité de Virologie et Immunologie Moléculaires (VIM, UMR892), INRAE, Université Paris-Saclay, 78352 Jouy-en-Josas, France., Anson B; Janssen Research & Development LLC, Spring House (PA 19477) And Brisbane (CA 94005), USA., de Bruyn S; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Verheyen N; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Thys K; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Conceição-Neto N; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Van Ginderen M; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Kwanten L; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Ysebaert N; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Vranckx L; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Peeters E; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Lanckacker E; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Gallup JM; Iowa State University, Ames, IA 50011, USA., Sitthicharoenchai P; Iowa State University, Ames, IA 50011, USA., Alnajjar S; Iowa State University, Ames, IA 50011, USA., Ackermann MR; Iowa State University, Ames, IA 50011, USA., Adhikary S; Janssen Research & Development LLC, Spring House (PA 19477) And Brisbane (CA 94005), USA., Bhaumik A; Janssen Research & Development LLC, Spring House (PA 19477) And Brisbane (CA 94005), USA., Patrick A; Janssen Research & Development LLC, Spring House (PA 19477) And Brisbane (CA 94005), USA., Fung A; Janssen Research & Development LLC, Spring House (PA 19477) And Brisbane (CA 94005), USA., Sutto-Ortiz P; AFMB, Aix-Marseille University, CNRS UMR 7257, 163 Avenue de Luminy, Marseille, France., Decroly E; AFMB, Aix-Marseille University, CNRS UMR 7257, 163 Avenue de Luminy, Marseille, France., Mason SW; Janssen Research & Development LLC, Spring House (PA 19477) And Brisbane (CA 94005), USA., Lançois D; Janssen France, 27106 Val de Reuil, France., Deval J; Janssen Research & Development LLC, Spring House (PA 19477) And Brisbane (CA 94005), USA., Jin Z; Janssen Research & Development LLC, Spring House (PA 19477) And Brisbane (CA 94005), USA., Eléouët JF; Unité de Virologie et Immunologie Moléculaires (VIM, UMR892), INRAE, Université Paris-Saclay, 78352 Jouy-en-Josas, France., Fearns R; Department of Virology, Immunology & Microbiology, National Emerging Infectious Diseases Laboratories, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA., Koul A; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: akoul@its.jnj.com., Roymans D; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Rigaux P; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium., Herschke F; Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium. Electronic address: fherschk@its.jnj.com.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2024 Jul; Vol. 227, pp. 105907. Date of Electronic Publication: 2024 May 19.
DOI: 10.1016/j.antiviral.2024.105907
Abstrakt: 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.
Competing Interests: Declaration of competing interest The following authors were employees of Johnson & Johnson (the sponsor of the work) at the time when the described work was performed, and may hold Johnson & Johnson shares: BA, SdB, NV, KT, NCN, MVG, LK, NY, LV, EP, EL, AB, AP, AF, SWM, DL, JD, ZJ, AK, DR, PR, FH. The work of the other authors on this project was funded by Johnson & Johnson. BB is an employee of Antwerpen University and received funding from Johnson & Johnson and from Flanders Innovation & Entrepreneurship organization (VLAIO, HBC.2019.2157) for this work.RF has a sponsored research agreement with Merck & Co unrelated to the work presented here.
(Copyright © 2024 Janssen Pharmaceutica NV. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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