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. 2024 Apr 22;16(4):651.
doi: 10.3390/v16040651.

Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections

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 Patel  1 , James J Kohler  1 , Manoj Bhasin  2 , Brian S Dobosh  2 , Vikas Sukhatme  3 , Rabindra M Tirouvanziam  2 , Raymond F Schinazi  1
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Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections

Selwyn J Hurwitz et al. Viruses. .

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; antiviral agents; coronavirus; drug repurposing; pharmacokinetics; potency; potential efficacy.

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Conflict of interest statement

R.F.S. has received royalties from Ely Lilly from the sales of baricitinib, used for the treatment of COVID-19. RFS received research funding from Pfizer for his group at Emory University. Emory University has reviewed and approved his conflict of interest. Other authors have no conflicts of interest to declare regarding this manuscript.

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