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Viruses ; 16(4)2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38675992

RESUMEN

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.


Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , Reposicionamiento de Medicamentos , SARS-CoV-2 , Antivirales/uso terapéutico , Antivirales/farmacología , Humanos , SARS-CoV-2/efectos de los fármacos , Chlorocebus aethiops , Células Vero , Células CACO-2 , Animales , COVID-19/virología
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