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

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 anti-cytopathic 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.

SUBMITTER: Zaliani A

PROVIDER: S-EPMC9279437 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Zaliani Andrea A Vangeel Laura L Reinshagen Jeanette J Iaconis Daniela D Kuzikov Maria M Keminer Oliver O Wolf Markus M Ellinger Bernhard B Esposito Francesca F Corona Angela A Tramontano Enzo E Manelfi Candida C Herzog Katja K Jochmans Dirk D De Jonghe Steven S Chiu Winston W Francken Thibault T Schepers Joost J Collard Caroline C Abbasi Kayvan K Claussen Carsten C Summa Vincenzo V Beccari Andrea R AR Neyts Johan J Gribbon Philip P Leyssen Pieter P

Scientific data 20220713 1

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) aime ...[more]

PMID: 35831315

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Project description:BackgroundThe coronaviruses (CoVs) called the attention of the world for causing outbreaks of severe acute respiratory syndrome (SARS-CoV), in Asia in 2002-03, and respiratory disease in the Middle East (MERS-CoV), in 2012. In December 2019, yet again a new coronavirus (SARS-CoV-2) first identified in Wuhan, China, was associated with a severe respiratory infection, known today as COVID-19. This new virus quickly spread throughout China and 30 additional countries. As result, the World Health Organization (WHO) elevated the status of the COVID-19 outbreak from emergency of international concern to pandemic on March 11, 2020. The impact of COVID-19 on public health and economy fueled a worldwide race to approve therapeutic and prophylactic agents, but so far, there are no specific antiviral drugs or vaccines available. In current scenario, the development of in vitro systems for viral mass production and for testing antiviral and vaccine candidates proves to be an urgent matter.ObjectiveThe objective of this paper is study the biology of SARS-CoV-2 in Vero-E6 cells at the ultrastructural level.MethodsIn this study, we documented, by transmission electron microscopy and real-time reverse transcription polymerase chain reaction (RT-PCR), the infection of Vero-E6 cells with SARS-CoV-2 samples isolated from Brazilian patients.FindingsThe infected cells presented cytopathic effects and SARS-CoV-2 particles were observed attached to the cell surface and inside cytoplasmic vesicles. The entry of the virus into cells occurred through the endocytic pathway or by fusion of the viral envelope with the cell membrane. Assembled nucleocapsids were verified inside rough endoplasmic reticulum cisterns (RER). Viral maturation seemed to occur by budding of viral particles from the RER into smooth membrane vesicles.Main conclusionsTherefore, the susceptibility of Vero-E6 cells to SARS-CoV-2 infection and the viral pathway inside the cells were demonstrated by ultrastructural analysis.

Dataset Information

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

Publications

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

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