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

Consistent with this hypothesis, we found that several molecules with potent EC 50 s were only able to inhibit replication to approximately 50-60 % at multiple high concentrations, including MLN-3897, YH-1238 and SL-11128 ( Figure 3A and Figure S5 ). While this may represent the maximal ability of these molecules to suppress viral replication, alternatively, analysis of these molecules utilizing lower MOIs at later timepoint may reveal greater inhibition of infection. In addition, validation assays were conducted employing drug concentrations that were half of what was utilized in the screen (2.5 µM versus 5 µM) and using a second isolate of SARS-CoV-2. The introduction of these stringencies during the validation step, as well as false positive activities from the HTS assay, likely account for ~30 % confirmation rate observed at this step of the analysis.