Fig. 1: High-throughput ReFRAME collection drug repositioning screen for SARS-CoV-2 antiviral compounds.

a, A schematic of the screening strategy used for the repositioning analysis of the ReFRAME library. Classification of the approximately 12,000 compounds in the ReFRAME collection across different stages of clinical development is depicted in the pie chart. For the HTS, compounds were pre-spotted in 384-well plates at a final concentration of 5 μM. Next, 3,000 Vero E6 cells were added to each well and pre-incubated with each compound for 16 h, followed by infection with a clinical isolate of SARS-CoV-2 (HKU-001a) with a MOI of 0.01. ATP levels in each well were measured 72 h after infection using a Cell Titer Glo viability assay as a surrogate measurement of viral CPE. b, Z-scores after normalization to the median of each plate for all positive (APY0201) and negative (DMSO) controls, as well as for non-infected cells, across all the screening plates. Data are mean ± s.d. for at least 376 independent wells. c, Correlation plot indicates the activity (Z-score) of each compound in the two replicate screens. d, The activity distribution of each compound based on the average of the Z-score of each replicate. Each dot indicates the average Z-score of the screening replicates for each drug (black dots). Values corresponding to DMSO (orange dots), APY0201 (cyan dots) and non-infected cells (purple dots) are also represented. R² indicates the linear correlation coefficients for the replicates (c).