tetano
Editor, Senior Moderator
Sci Data
. 2021 Feb 26;8(1):70.
doi: 10.1038/s41597-021-00848-4.
A SARS-CoV-2 cytopathicity dataset generated by high-content screening of a large drug repurposing collection
Bernhard Ellinger[SUP] #[/SUP][SUP] 1 [/SUP], Denisa Bojkova[SUP] #[/SUP][SUP] 2 [/SUP], Andrea Zaliani[SUP] 3 [/SUP], Jindrich Cinatl[SUP] 2 [/SUP], Carsten Claussen[SUP] 3 4 [/SUP], Sandra Westhaus[SUP] 2 [/SUP], Oliver Keminer[SUP] 3 [/SUP], Jeanette Reinshagen[SUP] 3 [/SUP], Maria Kuzikov[SUP] 3 [/SUP], Markus Wolf[SUP] 3 [/SUP], Gerd Geisslinger[SUP] 5 6 4 [/SUP], Philip Gribbon[SUP] 3 4 [/SUP], Sandra Ciesek[SUP] 2 6 7 [/SUP]
Affiliations
Abstract
SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic, in which acute respiratory infections are associated with high socio-economic burden. We applied high-content screening to a well-defined collection of 5632 compounds including 3488 that have undergone previous clinical investigations across 600 indications. The compounds were screened by microscopy for their ability to inhibit SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2. The primary screen identified 258 hits that inhibited cytopathicity by more than 75%, most of which were not previously known to be active against SARS-CoV-2 in vitro. These compounds were tested in an eight-point dose response screen using the same image-based cytopathicity readout. For the 67 most active molecules, cytotoxicity data were generated to confirm activity against SARS-CoV-2. We verified the ability of known inhibitors camostat, nafamostat, lopinavir, mefloquine, papaverine and cetylpyridinium to reduce the cytopathic effects of SARS-CoV-2, providing confidence in the validity of the assay. The high-content screening data are suitable for reanalysis across numerous drug classes and indications and may yield additional insights into SARS-CoV-2 mechanisms and potential therapeutic strategies.
. 2021 Feb 26;8(1):70.
doi: 10.1038/s41597-021-00848-4.
A SARS-CoV-2 cytopathicity dataset generated by high-content screening of a large drug repurposing collection
Bernhard Ellinger[SUP] #[/SUP][SUP] 1 [/SUP], Denisa Bojkova[SUP] #[/SUP][SUP] 2 [/SUP], Andrea Zaliani[SUP] 3 [/SUP], Jindrich Cinatl[SUP] 2 [/SUP], Carsten Claussen[SUP] 3 4 [/SUP], Sandra Westhaus[SUP] 2 [/SUP], Oliver Keminer[SUP] 3 [/SUP], Jeanette Reinshagen[SUP] 3 [/SUP], Maria Kuzikov[SUP] 3 [/SUP], Markus Wolf[SUP] 3 [/SUP], Gerd Geisslinger[SUP] 5 6 4 [/SUP], Philip Gribbon[SUP] 3 4 [/SUP], Sandra Ciesek[SUP] 2 6 7 [/SUP]
Affiliations
- PMID: 33637768
- DOI: 10.1038/s41597-021-00848-4
Abstract
SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic, in which acute respiratory infections are associated with high socio-economic burden. We applied high-content screening to a well-defined collection of 5632 compounds including 3488 that have undergone previous clinical investigations across 600 indications. The compounds were screened by microscopy for their ability to inhibit SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2. The primary screen identified 258 hits that inhibited cytopathicity by more than 75%, most of which were not previously known to be active against SARS-CoV-2 in vitro. These compounds were tested in an eight-point dose response screen using the same image-based cytopathicity readout. For the 67 most active molecules, cytotoxicity data were generated to confirm activity against SARS-CoV-2. We verified the ability of known inhibitors camostat, nafamostat, lopinavir, mefloquine, papaverine and cetylpyridinium to reduce the cytopathic effects of SARS-CoV-2, providing confidence in the validity of the assay. The high-content screening data are suitable for reanalysis across numerous drug classes and indications and may yield additional insights into SARS-CoV-2 mechanisms and potential therapeutic strategies.