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Evaluation of drugs for potential repurposing against COVID-19 using a tier-based scoring system
Jarvis, M. A. Hansen, F. A. Rosenke, K. Haddock, E. Rollinson, C. Rule, S. Sewell, G. Hughes, Andrew Feldmann, H.
Jarvis, M. A.
Hansen, F. A.
Rosenke, K.
Haddock, E.
Rollinson, C.
Rule, S.
Sewell, G.
Hughes, Andrew
Feldmann, H.
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Abstract
Background: As the Coronavirus Disease 2019 (COVID-19) pandemic grows daily, we remain with no prophylactic and only minimal therapeutic interventions to prevent or ameliorate severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Prior to SARS-CoV-2 emergence, high throughput screens utilizing clinically developed drugs identified compounds with in vitro inhibitory effect on human coronaviruses that may have potential for repurposing as treatment options for COVID-19. However, caution should be applied to repurposing of these drugs when they are taken out of context of human pharmacokinetic parameters associated with normal therapeutic use.
Methods: Our aim was to provide a tier-based scoring system to interrogate this data set and match each drug with its human pharmacokinetic criteria, such as route of administration, therapeutic plasma levels and half-life, tissue distribution, and safety.
Results: Our analysis excluded most previously identified drugs but identified members of 4 drug classes (antimalarial amino-quinolones, selective estrogen receptor modulators; SERMs, low potency tricyclic antipsychotics and tricyclic antidepressants) as potential drug candidates for COVID-19. Two of them, the tricyclic antipsychotics and tricyclic antidepressants were further excluded based on a high adverse event profile.
Conclusions: In summary, our findings using a new pharmacokinetic-based scoring system supports efficacy testing of only a minority of candidates against SARS-CoV-2 infection.
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2020
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Jarvis MA, Hansen FA, Rosenke K, Haddock E, Rollinson C, Rule S, et al. Evaluation of drugs for potential repurposing against COVID-19 using a tier-based scoring system. Antivir Ther. 2020.