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.
【저자키워드】 SARS-CoV-2, Chloroquine, Hydroxychloroquine, deep learning, Remdesivir, Drug screening, Emetine, Deep transfer learning, 【초록키워드】 COVID-19, viruses, pandemic, Antiviral, drugs, Toxicity, Screening, antiviral drug, Microscopy, implementation, cell death, quantification, Coronavirus-2, CPE, Cytopathic effect, Concentration, Image, virus titer, acute respiratory syndrome, inhibitory effect, transfer, monolayer, approach, fine-tune, responsible, include, provided, cause, in vitro experiments, accelerate, DTL, TOX, 【제목키워드】 drug, inhibition, learning, Recognition, deep, Automatic,