tetano
Editor, Senior Moderator
J Med Virol
. 2022 Feb 28.
doi: 10.1002/jmv.27683. Online ahead of print.
Development and optimisation of a high-throughput screening assay for in vitro anti-SARS-CoV-2 activity: evaluation of 5676 phase 1 passed structures
Winston Chiu[SUP] 1 [/SUP], Lore Verschueren[SUP] 2 [/SUP], Christel Van den Eynde[SUP] 2 [/SUP], Christophe Buyck[SUP] 2 [/SUP], Sandra De Meyer[SUP] 2 [/SUP], Dirk Jochmans[SUP] 1 [/SUP], Denisa Bojkova[SUP] 3 [/SUP], Sandra Ciesek[SUP] 3 [/SUP], Jindrich Cinatl[SUP] 3 [/SUP], Steven De Jonghe[SUP] 1 [/SUP], Pieter Leyssen[SUP] 1 [/SUP], Johan Neyts[SUP] 1 [/SUP], Marnix Van Loock[SUP] 2 [/SUP], Ellen Van Damme[SUP] 2 [/SUP]
Affiliations
Abstract
Although vaccines are currently used to control the coronavirus disease 2019 (COVID-19) pandemic, treatment options are urgently needed for those who cannot be vaccinated and for future outbreaks involving new severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) strains or coronaviruses not covered by current vaccines. Thus far, few existing antivirals are known to be effective against SARS-CoV-2 and clinically successful against COVID-19. As part of an immediate response to the COVID-19 pandemic, a high-throughput, high content imaging-based SARS-CoV-2 infection assay was developed in VeroE6-eGFP cells and was used to screen a library of 5676 compounds that passed phase 1 clinical trials. Eight drugs (nelfinavir, RG-12915, itraconazole, chloroquine, hydroxychloroquine, sematilide, remdesivir, and doxorubicin) were identified as inhibitors of in vitro anti-SARS-CoV-2 activity in VeroE6-eGFP and/or Caco-2 cell lines. However, apart from remdesivir, toxicity and pharmacokinetic data did not support further clinical development of these compounds for COVID-19 treatment. This article is protected by copyright. All rights reserved.
Keywords: SARS Coronavirus; antiviral agents; coronavirus.
. 2022 Feb 28.
doi: 10.1002/jmv.27683. Online ahead of print.
Development and optimisation of a high-throughput screening assay for in vitro anti-SARS-CoV-2 activity: evaluation of 5676 phase 1 passed structures
Winston Chiu[SUP] 1 [/SUP], Lore Verschueren[SUP] 2 [/SUP], Christel Van den Eynde[SUP] 2 [/SUP], Christophe Buyck[SUP] 2 [/SUP], Sandra De Meyer[SUP] 2 [/SUP], Dirk Jochmans[SUP] 1 [/SUP], Denisa Bojkova[SUP] 3 [/SUP], Sandra Ciesek[SUP] 3 [/SUP], Jindrich Cinatl[SUP] 3 [/SUP], Steven De Jonghe[SUP] 1 [/SUP], Pieter Leyssen[SUP] 1 [/SUP], Johan Neyts[SUP] 1 [/SUP], Marnix Van Loock[SUP] 2 [/SUP], Ellen Van Damme[SUP] 2 [/SUP]
Affiliations
- PMID: 35229317
- DOI: 10.1002/jmv.27683
Abstract
Although vaccines are currently used to control the coronavirus disease 2019 (COVID-19) pandemic, treatment options are urgently needed for those who cannot be vaccinated and for future outbreaks involving new severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) strains or coronaviruses not covered by current vaccines. Thus far, few existing antivirals are known to be effective against SARS-CoV-2 and clinically successful against COVID-19. As part of an immediate response to the COVID-19 pandemic, a high-throughput, high content imaging-based SARS-CoV-2 infection assay was developed in VeroE6-eGFP cells and was used to screen a library of 5676 compounds that passed phase 1 clinical trials. Eight drugs (nelfinavir, RG-12915, itraconazole, chloroquine, hydroxychloroquine, sematilide, remdesivir, and doxorubicin) were identified as inhibitors of in vitro anti-SARS-CoV-2 activity in VeroE6-eGFP and/or Caco-2 cell lines. However, apart from remdesivir, toxicity and pharmacokinetic data did not support further clinical development of these compounds for COVID-19 treatment. This article is protected by copyright. All rights reserved.
Keywords: SARS Coronavirus; antiviral agents; coronavirus.