More than efficacy revealed by single-cell analysis of antiviral therapeutics

Wu Liu; Mehmet U. Caglar; Zhangming Mao; Andrew Woodman; Jamie J. Arnold; Claus O. Wilke; Craig E. Cameron

This study was designed to determine the extent to which single-cell analysis of antiviral 55 agents can contribute to our understanding of antiviral therapeutics relative to traditional 56 approaches. We describe a microfluidics device that can be used to produce complete dose-57 response curves. We have used this device to compare three, mechanistically-distinct classes of 58 antiviral agents: a PV polymerase inhibitor (2'-C-methyl-adenosine, 2'-C-Me-A); a PV protease 59 inhibitor (rupintrivir); and two HSP90 inhibitors (geldanamycin, GA, and ganetespib, GS). We 60 find that single-cell analysis distinguishes these classes of inhibitors. We suggest that addition of 61 single-cell analysis to the existing paradigm for preclinical development of antiviral therapies 62 may have the potential to identify leads with limited potential for development of resistance. 63 All rights reserved. No reuse allowed without permission.