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. Epub 2024 May 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Drug Resistance, Viral
  • Humans
  • Lung / virology
  • Respiratory Syncytial Virus Infections* / drug therapy
  • Respiratory Syncytial Virus Infections* / virology
  • Respiratory Syncytial Virus, Human* / drug effects
  • Sheep
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication* / drug effects

Substances

  • Antiviral Agents
  • Viral Proteins