Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors.

ABSTRACT: Respiratory syncytial virus (RSV) is a leading pediatric pathogen that is responsible for a majority of infant hospitalizations due to viral disease. Despite its clinical importance, no vaccine prophylaxis against RSV disease or effective antiviral therapeutic is available. In this study, we established a robust high-throughput drug screening protocol by using a recombinant RSV reporter virus to expand the pool of RSV inhibitor candidates. Mechanistic characterization revealed that a potent newly identified inhibitor class blocks viral entry through specific targeting of the RSV fusion (F) protein. Resistance against this class was induced and revealed overlapping hotspots with diverse, previously identified RSV entry blockers at different stages of preclinical and clinical development. A

SUBMITTER: Yan D 

PROVIDER: S-EPMC4143008 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature