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

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    Authors
    Jarvis, M. A.
    Hansen, F. A.
    Rosenke, K.
    Haddock, E.
    Rollinson, C.
    Rule, S.
    Sewell, G.
    Hughes, Andrew
    Feldmann, H.
    Affiliation
    University of Plymouth, Plymouth, Devon, UK.
    Issue Date
    2020
    
    Metadata
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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.
    Citation
    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.
    Journal
    Antiviral Therapy
    URI
    http://hdl.handle.net/10541/623252
    DOI
    10.3851/imp3368
    PubMed ID
    32744511
    Additional Links
    https://dx.doi.org/10.3851/imp3368
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.3851/imp3368
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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