id author title date pages extension mime words sentences flesch summary cache txt cord-296649-h6oyjz56 Scherf-Clavel, Oliver Tissue Level Profiling of SARS-CoV-2 antivirals in mice to predict their effects: comparing Remdesivir’s active metabolite GS-441 524 vs. the clinically failed Hydroxychloroquine 2020-11-06 .txt text/plain 5076 263 53 In this study, an adapted mouse model was chosen to demonstrate its suitability to provide sufficient information on the model substances GS-441 524 and HCQ regarding plasma concentration and distribution into relevant tissues a prerequisite for treatment effectiveness. Blood and organ samples were taken at several time points and drug concentrations were quantified in plasma and tissue homogenates by two liquid chromatography/tandem mass spectrometry methods. For GS-441 524, measured tissue concentrations exceeded the reported in vitro EC50 values by more than 10-fold and in consideration of its high efficacy against feline infectious peritonitis, GS-441 524 could indeed be effective against SARS-CoV-2 in vivo. The value obtained from our experiments falls in that range and is comparable to the V z obtained in mice from blood concentrations and to plasma V z measured in humans (see Table 4 ). ./cache/cord-296649-h6oyjz56.txt ./txt/cord-296649-h6oyjz56.txt