tetano
Editor, Senior Moderator
Antivir Ther
. 2020 Aug 3.
doi: 10.3851/IMP3368. Online ahead of print.
Evaluation of drugs for potential repurposing against COVID-19 using a tier-based scoring system
Michael A Jarvis[SUP] 1 2 [/SUP], Frederick A Hansen[SUP] 3 [/SUP], Kyle Rosenke[SUP] 3 [/SUP], Elaine Haddock[SUP] 3 [/SUP], Christopher Rollinson[SUP] 4 [/SUP], Simon Rule[SUP] 4 [/SUP], Graham Sewell[SUP] 5 [/SUP], Andrew Hughes[SUP] 6 [/SUP], Heinz Feldmann[SUP] 3 [/SUP]
Affiliations
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.
. 2020 Aug 3.
doi: 10.3851/IMP3368. Online ahead of print.
Evaluation of drugs for potential repurposing against COVID-19 using a tier-based scoring system
Michael A Jarvis[SUP] 1 2 [/SUP], Frederick A Hansen[SUP] 3 [/SUP], Kyle Rosenke[SUP] 3 [/SUP], Elaine Haddock[SUP] 3 [/SUP], Christopher Rollinson[SUP] 4 [/SUP], Simon Rule[SUP] 4 [/SUP], Graham Sewell[SUP] 5 [/SUP], Andrew Hughes[SUP] 6 [/SUP], Heinz Feldmann[SUP] 3 [/SUP]
Affiliations
- PMID: 32744511
- 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.