| Title | Prospects for the development of fusion inhibitors to treat human respiratory syncytial virus infection. | | Author(s) | Bonfanti JF, Roymans D | | Institution | Tibotec, a Division of Janssen-Cilag, Department of Medicinal Chemistry, Campus de Maigremont-BP615, F-27106 Val de Reuil Cedex, France. jbonfant@its.jnj.com. | | Source | Curr Opin Drug Discov Devel 2009 Jul; 12(4):479-87. | | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19562644 |
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