Cytopathic SARS-CoV-2 screening on VERO-E6 cells in a large-scale repurposing effort

Andrea Zaliani;Laura Vangeel;Jeanette Reinshagen;Daniela Iaconis;Maria Kuzikov;Oliver Keminer;Markus Wolf;Bernhard Ellinger;Francesca Esposito;Angela Corona;Enzo Tramontano;Candida Manelfi;Katja Herzog;Dirk Jochmans;Steven De Jonghe;Winston Chiu;Thibault Francken;Joost Schepers;Caroline Collard;Kayvan Abbasi;Carsten Claussen;Vincenzo Summa;Andrea R. Beccari;Johan Neyts;Philip Gribbon;Pieter Leyssen

2022-01-01

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Abstract

Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anticytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.