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Antiviral Res
. 2023 Dec 27:105789.
doi: 10.1016/j.antiviral.2023.105789. Online ahead of print. A flexible, image-based, high-throughput platform encompassing in-depth cell profiling to identify broad-spectrum coronavirus antivirals with limited off-target effects
Jordi Doijen 1 , Inha Heo 2 , Koen Temmerman 3 , Peter Vermeulen 4 , Annick Diels 5 , Steffen Jaensch 6 , Mark Burcin 7 , Nick Van den Broeck 8 , Valerie Raeymaekers 9 , Joren Peremans 10 , Katrien Konings 11 , Maxime Clement 12 , Danielle Peeters 13 , Marnix Van Loock 14 , Anil Koul 15 , Christophe Buyck 16 , Michiel Van Gool 17 , Ellen Van Damme 18
Affiliations
The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a major threat to global health. Although the World Health Organization ended the public health emergency status, antiviral drugs are needed to address new variants of SARS-CoV-2 and future pandemics. To identify novel broad-spectrum coronavirus drugs, we developed a high-content imaging platform compatible with high-throughput screening. The platform is broadly applicable as it can be adapted to include various cell types, viruses, antibodies, and dyes. We demonstrated that the antiviral activity of compounds against SARS-CoV-2 variants (Omicron BA.5 and Omicron XBB.1.5), SARS-CoV, and human coronavirus 229E could easily be assessed. The inclusion of cellular dyes and immunostaining in combination with in-depth image analysis enabled us to identify compounds that induced undesirable phenotypes in host cells, such as changes in cell morphology or in lysosomal activity. With the platform, we screened ∼900K compounds and triaged hits, thereby identifying potential candidate compounds carrying broad-spectrum activity with limited off-target effects. The flexibility and early-stage identification of compounds with limited host cell effects provided by this high-content imaging platform can facilitate coronavirus drug discovery. We anticipate that its rapid deployability and fast turnaround can also be applied to combat future pandemics.
Keywords: Antivirals; Coronavirus; Drug discovery; High throughput; High-content imaging; Phenotypic screening.
. 2023 Dec 27:105789.
doi: 10.1016/j.antiviral.2023.105789. Online ahead of print. A flexible, image-based, high-throughput platform encompassing in-depth cell profiling to identify broad-spectrum coronavirus antivirals with limited off-target effects
Jordi Doijen 1 , Inha Heo 2 , Koen Temmerman 3 , Peter Vermeulen 4 , Annick Diels 5 , Steffen Jaensch 6 , Mark Burcin 7 , Nick Van den Broeck 8 , Valerie Raeymaekers 9 , Joren Peremans 10 , Katrien Konings 11 , Maxime Clement 12 , Danielle Peeters 13 , Marnix Van Loock 14 , Anil Koul 15 , Christophe Buyck 16 , Michiel Van Gool 17 , Ellen Van Damme 18
Affiliations
- PMID: 38158129
- DOI: 10.1016/j.antiviral.2023.105789
The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a major threat to global health. Although the World Health Organization ended the public health emergency status, antiviral drugs are needed to address new variants of SARS-CoV-2 and future pandemics. To identify novel broad-spectrum coronavirus drugs, we developed a high-content imaging platform compatible with high-throughput screening. The platform is broadly applicable as it can be adapted to include various cell types, viruses, antibodies, and dyes. We demonstrated that the antiviral activity of compounds against SARS-CoV-2 variants (Omicron BA.5 and Omicron XBB.1.5), SARS-CoV, and human coronavirus 229E could easily be assessed. The inclusion of cellular dyes and immunostaining in combination with in-depth image analysis enabled us to identify compounds that induced undesirable phenotypes in host cells, such as changes in cell morphology or in lysosomal activity. With the platform, we screened ∼900K compounds and triaged hits, thereby identifying potential candidate compounds carrying broad-spectrum activity with limited off-target effects. The flexibility and early-stage identification of compounds with limited host cell effects provided by this high-content imaging platform can facilitate coronavirus drug discovery. We anticipate that its rapid deployability and fast turnaround can also be applied to combat future pandemics.
Keywords: Antivirals; Coronavirus; Drug discovery; High throughput; High-content imaging; Phenotypic screening.