Viruses, Vol. 16, Pages 651: Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections

Viruses, Vol. 16, Pages 651: Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections Viruses doi: 10.3390/v16040651 Authors: Selwyn J. Hurwitz Ramyani De Julia C. LeCher Jessica A. Downs-Bowen Shu Ling Goh Keivan Zandi Tamara McBrayer Franck Amblard Dharmeshkumar J. Patel James J. Kohler Manoj Bhasin Brian S. Dobosh Vikas Sukhatme Rabindra M. Tirouvanziam Raymond F. Schinazi Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC50, CC50) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (Cmax)/EC50, 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 CC50 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 Cmax/EC50 ≥ 6.8 in Calu-3 or Caco-2 cells. EC50 of nucleoside analogs were cell dependent. This approach and earlier availability of more relevant cultures could have reduced the number of unwarranted clinical trials.
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research