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Development and optimisation of a high-throughput screening assay for in vitro antiSARS-CoV-2 activity: evaluation of 5676 phase 1 passed structures

  • 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 candidates (nelfinavir, RG-12915, itraconazole, chloroquine, hydroxychloroquine, sematilide, remdesivir, and doxorubicin) with in vitro anti–SARS-CoV-2 activity in VeroE6-eGFP and/or Caco-2 cell lines were identified. However, apart from remdesivir, toxicity and pharmacokinetic data did not support further clinical development of these compounds for COVID-19 treatment.

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Author:Winston ChiuORCiD, Lore Verschueren, Christel van der Eynde, Christophe BuyckORCiD, Sandra De MeyerORCiD, Dirk JochmansORCiDGND, Denisa BojkovaORCiDGND, Sandra CiesekORCiDGND, Jindrich CinatlORCiDGND, Steven De JongheORCiD, Pieter LeyssenORCiD, Johan NeytsORCiD, Marnix van LoockORCiD, Ellen van DammeORCiD
URN:urn:nbn:de:hebis:30:3-730138
DOI:https://doi.org/10.1101/2022.02.02.478671
Parent Title (English):bioRxiv
Document Type:Preprint
Language:English
Date of Publication (online):2022/02/03
Date of first Publication:2022/02/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/11/14
Issue:2022.02.02.478671
Page Number:32
HeBIS-PPN:513882588
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International