State of the Art in Respiratory Syncytial Virus Drug Discovery and Development

• Published in: Journal of medicinal chemistry Vol. 62; no. 7; pp. 3206 - 3227
• Main Authors: Cockerill, G. Stuart, Good, James A. D, Mathews, Neil
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 11-04-2019
• Subjects: Animals; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Drug Discovery; Humans; Nucleocapsid Proteins - chemistry; Nucleocapsid Proteins - metabolism; Palivizumab - immunology; Palivizumab - therapeutic use; Respiratory Syncytial Virus Infections - drug therapy; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus, Human - drug effects; Respiratory Syncytial Virus, Human - immunology; Respiratory Syncytial Virus, Human - metabolism; Small Molecule Libraries - chemistry; Small Molecule Libraries - metabolism; Small Molecule Libraries - therapeutic use; Viral Fusion Proteins - chemistry; Viral Fusion Proteins - metabolism
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.8b01361

Respiratory syncytial virus (RSV) is a globally prevalent viral infection with limited treatment options which hospitalizes millions each year. Treatment options have been limited to palivizumab, a monoclonal antibody, approved for prophylaxis in high-risk infants and ribavirin with very limited efficacy and significant safety concerns. This Perspective surveys the range of direct acting antiviral agents (DAAs) that target key steps in the viral life cycle. A number of approaches to DAAs have produced landmark clinical studies over the past few years, notably in fusion and nucleoside inhibitors, and an update of the clinical status of these compounds is provided. Non-nucleoside inhibitors of replication are reviewed in addition to inhibitors of other mechanisms, notably the RSV N and G proteins. This article will provide an informative perspective of the current status of drug discovery targeted at providing an effective therapy for RSV infection.