Michael A Jarvis1,2, Frederick A Hansen3, Kyle Rosenke3, Elaine Haddock3, Christopher Rollinson4, Simon Rule4, Graham Sewell5, Andrew Hughes6, Heinz Feldmann3. 1. University of Plymouth, Plymouth, Devon, UK. 2. The Vaccine Group, Ltd, Plymouth, Devon, UK. 3. Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. 4. University Hospitals Plymouth NHS Trust, Plymouth, Devon, UK. 5. The Leicester School of Pharmacy, De Montfort University, Leicester, UK. 6. Manchester Cancer Research Centre, University of Manchester, Manchester, UK.
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 four 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.
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 humancoronaviruses 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 (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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Authors: H Javelot; C Straczek; G Meyer; C Gitahy Falcao Faria; L Weiner; D Drapier; E Fakra; P Fossati; S Weibel; S Dizet; B Langrée; M Masson; R Gaillard; M Leboyer; P M Llorca; C Hingray; E Haffen; A Yrondi Journal: Encephale Date: 2021-09-02 Impact factor: 1.291
Authors: Kyle Rosenke; Atsushi Okumura; Matthew C Lewis; Friederike Feldmann; Kimberly Meade-White; W Forrest Bohler; Amanda Griffin; Rebecca Rosenke; Carl Shaia; Michael A Jarvis; Heinz Feldmann Journal: bioRxiv Date: 2022-02-23
Authors: Kyle Rosenke; Kimberly Meade-White; Michael Letko; Chad Clancy; Frederick Hansen; Yanan Liu; Atsushi Okumura; Tsing-Lee Tang-Huau; Rong Li; Greg Saturday; Friederike Feldmann; Dana Scott; Zhongde Wang; Vincent Munster; Michael A Jarvis; Heinz Feldmann Journal: bioRxiv Date: 2020-09-27