부산대학교 도서관

Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC[sub.50] , CC[sub.50] ) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (C[sub.max] )/EC[sub.50] , were used to predict the potential in vivo efficacy. The 20 drugs with the highest ratios were retested in human Calu-3 and Caco-2 cells, and their CC[sub.50] was determined in an expanded panel of cell lines. Many of the 20 drugs with the highest ratios were inactive in human Calu-3 and Caco-2 cells. Antivirals effective in controlled clinical trials had unbound C[sub.max] /EC[sub.50] ≥ 6.8 in Calu-3 or Caco-2 cells. EC[sub.50] of nucleoside analogs were cell dependent. This approach and earlier availability of more relevant cultures could have reduced the number of unwarranted clinical trials.
Author(s): Selwyn J. Hurwitz [1]; Ramyani De [1]; Julia C. LeCher [1]; Jessica A. Downs-Bowen [1]; Shu Ling Goh [1]; Keivan Zandi [1]; Tamara McBrayer [1]; Franck Amblard [1]; Dharmeshkumar [...]