Deep Transfer Learning Approach for Automatic Recognition of Drug Toxicity and Inhibition of SARS-CoV-2.

Journal: Viruses
PMID:

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.

Authors

  • Julia Werner
    Department of Molecular Medicine II, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
  • Raphael M Kronberg
    Department of Molecular Medicine II, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
  • Pawel Stachura
    Department of Molecular Medicine II, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
  • Philipp N Ostermann
    Institute of Virology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
  • Lisa Müller
    Institute of Virology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
  • Heiner Schaal
    Institute of Virology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
  • Sanil Bhatia
    Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
  • Jakob N Kather
    Department of Gastroenterology, University Hospital RWTH Aachen, Aachen, Germany. jakob.kather@gmail.com.
  • Arndt Borkhardt
    Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
  • Aleksandra A Pandyra
    Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
  • Karl S Lang
    Institute of Immunology, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany.
  • Philipp A Lang
    Department of Molecular Medicine II, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.