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Novel diversity-oriented synthesis-derived respiratory syncytial virus inhibitors identified via a high throughput replicon-based screen.


ABSTRACT: Respiratory syncytial virus (RSV) infections affect millions of children and adults every year. Despite the significant disease burden, there are currently no safe and effective vaccines or therapeutics. We employed a replicon-based high throughput screen combined with live-virus triaging assays to identify three novel diversity-oriented synthesis-derived scaffolds with activity against RSV. One of these small molecules is shown to target the RSV polymerase (L protein) to inhibit viral replication and transcription; the mechanisms of action of the other small molecules are currently unknown. The compounds described herein may provide attractive inhibitors for lead optimization campaigns.

SUBMITTER: Duvall JR 

PROVIDER: S-EPMC4937797 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Novel diversity-oriented synthesis-derived respiratory syncytial virus inhibitors identified via a high throughput replicon-based screen.

Duvall Jeremy R JR   VerPlank Lynn L   Ludeke Barbara B   McLeod Sarah M SM   Lee Maurice D MD   Vishwanathan Karthick K   Mulrooney Carol A CA   Le Quement Sebastian S   Yu Qin Q   Palmer Michelle A MA   Fleming Paul P   Fearns Rachel R   Foley Michael A MA   Scherer Christina A CA  

Antiviral research 20160406


Respiratory syncytial virus (RSV) infections affect millions of children and adults every year. Despite the significant disease burden, there are currently no safe and effective vaccines or therapeutics. We employed a replicon-based high throughput screen combined with live-virus triaging assays to identify three novel diversity-oriented synthesis-derived scaffolds with activity against RSV. One of these small molecules is shown to target the RSV polymerase (L protein) to inhibit viral replicati  ...[more]

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