Evaluation of drugs for Potential Repurposing against COVID-19 using a Tier-Based Scoring System. Issue 4 (May 2020)

• Record Type: Journal Article
• Authors: Jarvis, Michael A; Hansen, Frederick A; Rosenke, Kyle; Haddock, Elaine; Rollinson, Christopher; Rule, Simon; Sewell, Graham; Hughes, Andrew; Feldmann, Heinz
• Is Part Of: Antiviral therapy. Volume 25:Issue 4(2020)
• Page Start: 223
• Page End: 231
• Publication Date: 2020-05
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP3368
• Languages: English
• ISSNs: 1359-6535

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 Corona-virus 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 four drug classes (anti-malarial 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.