V I R O L O G Y 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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Because many aspects of viral infection dynamics and inhibition are governed by stochastic processes, single-cell analysis should provide more information than approaches using population averaging. We have developed a microfluidic device composed of ~6000 wells, with each well containing a microstructure to capture single, infected cells replicating an enterovirus expressing a fluorescent reporter protein. We have used this system to characterize enterovirus inhibitors with distinct mechanisms of action. Single-cell analysis reveals that each class of inhibitor interferes with the viral infection cycle in a manner that can be distinguished by principal component analysis. Single-cell analysis of antiviral candidates not only reveals efficacy but also facilitates clustering of drugs with the same mechanism of action and provides some indication of the ease with which resistance will develop.

Original languageEnglish (US)
Article numbereaax4761
JournalScience Advances
Volume5
Issue number10
DOIs
StatePublished - Oct 30 2019

All Science Journal Classification (ASJC) codes

  • General

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