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Evaluation of drugs for potential repurposing against COVID-19 using a tier-based scoring system

Michael A Jarvis, Frederick A Hansen, Kyle Rosenke, Elaine Haddock, Christopher Rollinson, Simon Rule, Graham Sewell, Andrew Hughes, Heinz Feldmann

Corresponding author name: Michael A Jarvis
Corresponding author e-mail: michael.jarvis@plymouth.ac.uk

doi: 10.3851/IMP3368

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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