Development and optimisation of a high-throughput screening assay for in vitro anti-SARS-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 coronaviruse...

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Published in:bioRxiv 2022-02
Main Authors: Chiu, Winston, Verschueren, Lore, Christel Van Den Eynde, Buyck, Christophe, De Meyer, Sandra, Jochmans, Dirk, Bojkova, Denisa, Ciesek, Sandra, Cinatl, Jindrich, De Jonghe, Steven, Leyssen, Pieter, Neyts, Johan, Marnix Van Loock, Ellen Van Damme
Format: Article
Language:English
Subjects:
Antiviral agents
Cell lines
Chloroquine
Clinical trials
Coronaviruses
COVID-19
COVID-19 vaccines
Doxorubicin
High-throughput screening
Hydroxychloroquine
Itraconazole
Nelfinavir
Pandemics
Pharmacokinetics
Severe acute respiratory syndrome coronavirus 2
Toxicity
Vaccines
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Summary: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. Competing Interest Statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SC received research funding from Janssen for this research. WC, DJ, SDJ, PL, and JN are employees from KU Leuven and received funding from Janssen for this research. LV, CVdE, CB, SDM, MVL, and EVD are employees of Janssen and may be stock owners of Johnson & Johnson. DB and JC have nothing to declare.
DOI:10.1101/2022.02.02.478671