A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals

Laura Riva; Shuofeng Yuan; Xin Yin; Laura Martin-Sancho; Naoko Matsunaga; Sebastian Burgstaller-Muehlbacher; Lars Pache; Paul P. De Jesus; Mitchell V. Hull; Max Chang; Jasper Fuk-Woo Chan; Jianli Cao; Vincent Kwok-Man Poon; Kristina Herbert; Tu-Trinh Nguyen; Yuan Pu; Courtney Nguyen; Andrey Rubanov; Luis Martinez-Sobrido; Wen-Chun Liu; Lisa Miorin; Kris M. White; Jeffrey R. Johnson; Christopher Benner; Ren Sun; Peter G. Schultz; Andrew Su; Adolfo Garcia-Sastre; Arnab K. Chatterjee; Kwok-Yung Yuen; Sumit K. Chanda

Repositioning analysis of the ReFRAME Drug Repurposing Library. Since the results of the LOPAC®1280 HTS analysis indicated that these assay conditions were suitable to progress to a large-scale screen, we used this experimental design to screen the comprehensive ReFRAME drug repurposing collection. This library is an inclusive collection of nearly 12,000 chemical compounds, that have been either FDA-approved or registered outside the US, entered clinical trials, or undergone significant pre-clinical characterization 27 . Specifically, 11,987 compounds were arrayed in 384-well plates at a final concentration of 5 µM. As with the previous assay, Vero E6 cells were seeded into each well pre-spotted with compound, infected 16 h later with SARS-CoV-2 (MOI = 0.01) and at 72 hours post-infection, CPE was determined. Analysis of the average Zʹ factor calculated on the activity of APY0201 was determined to be 0.51, reflecting an acceptable assay dynamic range ( Figure 1C, left panel) . The screen was then repeated as an independent replicate and the correlation coefficient (R 2 ) for the two replicates was determined to be 0.68 ( Figure 1C Based on a nominal P-value cutoff of 0.05 and FDR q-value < 0.25, we found that author/funder. All rights reserved. No reuse allowed without permission.