Deep transfer learning approach for automatic recognition of drug toxicity and inhibition of sars-cov-2

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Julia Werner - , Heinrich Heine University Düsseldorf (Author)
  • Raphael M. Kronberg - , Heinrich Heine University Düsseldorf (Author)
  • Pawel Stachura - , Heinrich Heine University Düsseldorf (Author)
  • Philipp N. Ostermann - , Heinrich Heine University Düsseldorf (Author)
  • Lisa Müller - , Heinrich Heine University Düsseldorf (Author)
  • Heiner Schaal - , Heinrich Heine University Düsseldorf (Author)
  • Sanil Bhatia - , Heinrich Heine University Düsseldorf (Author)
  • Jakob N. Kather - , RWTH Aachen University (Author)
  • Arndt Borkhardt - , Heinrich Heine University Düsseldorf (Author)
  • Aleksandra A. Pandyra - , Heinrich Heine University Düsseldorf (Author)
  • Karl S. Lang - , University of Duisburg-Essen (Author)
  • Philipp A. Lang - , Heinrich Heine University Düsseldorf (Author)

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes COVID-19 and is responsible for the ongoing pandemic. Screening of potential antiviral drugs against SARS-CoV-2 depend on in vitro experiments, which are based on the quantification of the virus titer. Here, we used virus-induced cytopathic effects (CPE) in brightfield microscopy of SARS-CoV-2-infected monolayers to quantify the virus titer. Images were classified using deep transfer learning (DTL) that fine-tune the last layers of a pre-trained Resnet18 (ImageNet). To exclude toxic concentrations of potential drugs, the network was expanded to include a toxic score (TOX) that detected cell death (CPETOXnet). With this analytic tool, the inhibitory effects of chloroquine, hydroxychloroquine, remdesivir, and emetine were validated. Taken together we developed a simple method and provided open access implementation to quantify SARS-CoV-2 titers and drug toxicity in experimental settings, which may be adaptable to assays with other viruses. The quantification of virus titers from brightfield images could accelerate the experimental approach for antiviral testing.

Details

Original languageEnglish
Article number610
JournalViruses
Volume13
Issue number4
Publication statusPublished - Apr 2021
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 33918368

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • Chloroquine, Deep learning, Deep transfer learning, Drug screening, Emetine, Hydroxychloroquine, Remdesivir, SARS-CoV-2