Prospects for the development of fusion inhibitors to treat human respiratory syncytial virus infection

Curr Opin Drug Discov Devel. 2009 Jul;12(4):479-87.


Human respiratory syncytial virus (hRSV) is a significant cause of respiratory illness in at-risk pediatric patients, immunocompromised adults and the elderly. No vaccine is currently available for the virus and treatment options are limited to the prophylactic treatment of at-risk infants with the mAb palivizumab (Synagis) and to therapeutic intervention with the nucleoside analog ribavirin (Rebetol). The clinical use of these agents is limited and a need exists for more effective treatment for the at-risk population. The merging of viral and cellular membranes is a crucial event in the hRSV life cycle that enables the virus to enter a host cell. The multistep fusion process is facilitated by the substantial refolding of a trimeric class I fusion protein (F protein), which is the main target of fusion inhibitors. Several small-molecule fusion inhibitors have been discovered, of which some have progressed significantly in the drug development process. BTA-9881 (Biota Holdings Ltd/MedImmune) and TMC-353121 (Johnson & Johnson) are the most advanced of this drug class. In addition, progress has been made in the development of next-generation antibodies such as motavizumab (Numax; MedImmune). This review will discuss the status and latest developments of compounds and antibodies that inhibit hRSV fusion.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use
  • Clinical Trials as Topic
  • Drug Design*
  • Humans
  • Molecular Structure
  • Protein Folding
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Respiratory Syncytial Virus Infections / drug therapy*
  • Respiratory Syncytial Virus, Human / drug effects*
  • Respiratory Syncytial Virus, Human / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Small Molecule Libraries / therapeutic use
  • Viral Fusion Proteins / antagonists & inhibitors*


  • 2-(6-((2-(3-hydroxypropyl)-5-methylphenylamino)methyl)-2-(3-morpholin-4-ylpropylamino)benzoimidazol-1-ylmethyl)-6-methylpyridin-3-ol
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • Benzimidazoles
  • Pyridines
  • Small Molecule Libraries
  • Viral Fusion Proteins
  • motavizumab