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

To our knowledge, this study represents the first analysis of a range of antiviral 295 therapeutics on viral infection dynamics at the single-cell level. The resolution afforded by this 296 approach is unprecedented when compared to other cell-based approaches, which only provide a 297 measure of efficacy. Given the substantial effort required to go from compound to mechanism 298 using the traditional experimental paradigm, the ability of single-cell analysis to inform 299 mechanism should make this approach a welcome addition to the drug discovery and 300 development toolbox. It is not uncommon for analogues to be synthesized during the drug-301 development process that lose specificity or even function by a different mechanism of action, 302 single-cell analysis has the potential to reveal changes such as these at the start of the analysis 303 instead of much, much later in the development process. Finally, although we have used antiviral 304 agents to demonstrate the power of single-cell analysis, use of this technology and approach will 305 All rights reserved. No reuse allowed without permission.