RT Journal Article
SR Electronic
T1 LATE-BREAKING ABSTRACT: Effects of a single treatment with PC786, a novel inhibitor of respiratory syncytial virus replication, on viral load and biomarkers in fully differentiated human bronchial epithelial cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP OA4989
DO 10.1183/13993003.congress-2016.OA4989
VO 48
IS suppl 60
A1 Daniel Brookes
A1 Matthew Coates
A1 Heather Allen
A1 John Ayrton
A1 Amanda Davis
A1 Mark Hows
A1 Pete Strong
A1 Garth Rapeport
A1 Kazuhiro Ito
YR 2016
UL http://erj.ersjournals.com/content/48/suppl_60/OA4989.abstract
AB Addition of RSV A2 to fully-differentiated air-liquid interface cultured human bronchial epithelial cells resulted in a robust infection which generated amplified viral titres and measurable pro-inflammatory biomarkers. The novel first-in-class anti-RSV agent, PC786, showed a concentration dependent inhibition of RSV replication determined by plaque assay following a single apical treatment on Day 1 post-infection, reducing viral titres to below detectable limits the following day. Viral titres remained undetectable for 2 or 5 days when treated with either 0.1 or 0.5µg/ml of PC786, respectively. PCR products showed similar kinetics to the RSV virus titre determined by plaque assay. RSV A2 infection also induced several pro-inflammatory cytokines (RANTES, IL-6, IL-8, IP-10), mucin and double stranded DNA, a marker of epithelial cell injury. A single treatment of PC786 on Day 1 post infection delayed the expression of each of these biomarkers. In addition, a good correlation was found between PC786 content within cells and anti-viral activity determined by PCR in apical wash. Thus, PC786 showed rapid onset of action and produced sustained inhibition of RSV replication and associated biomarker expression following only a single treatment post infection, and the anti-viral activity was correlated well with PC786 content within cells. Therefore PC786 has the potential to be an effective treatment for RSV infection in humans, and the clear PK-PD relationship observed in this study has the potential to help to predict efficacy of PC786 by measuring local epithelial concentrations of the drug in vivo.