2024 journal article

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

ANTIVIRAL RESEARCH, 227.

By: B. Bonneux ^*, A. Shareef ^*, S. Tcherniuk ^*, B. Anson ^*, S. Bruyn ^*, N. Verheyen^*, K. Thys ^*, N. Conceicao-Neto ^* ...and 26 other authors, including 1 NC State author, M. Van Ginderen^*, L. Kwanten^*, N. Ysebaert ^*, L. Vranckx^*, E. Peeters^*, E. Lanckacker^*, J. Gallup^*, P. Sitthicharoenchai^* , S. Alnajjar ^*, M. Ackermann ^*, S. Adhikary, A. Bhaumik ^*, A. Patrick, A. Fung, P. Sutto-Ortiz, E. Decroly, S. Mason, D. Lancois, J. Deval, Z. Jin, J. Eleouet, R. Fearns, A. Koul, D. Roymans, P. Rigaux, F. Herschke

author keywords: Respiratory syncytial virus; Direct anti -viral; Non-nucleos(t)ide inhibitor; Viral polymerase; Connector domain

10.1016/j.antiviral.2024.105907

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doi.org (publisher)

UN Sustainable Development Goal Categories

3. Good Health and Well-being (OpenAlex)

Source: Web Of Science

Added: July 1, 2024

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 suggested JNJ-7184 binds RSV-L in the connector domain. JNJ-7184 prevented RSV replication and transcription by inhibiting initiation or early elongation. JNJ-7184 was effective in air-liquid interface cultures and therapeutically in neonatal lambs, acting to drastically reverse the appearance of lung pathology.