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 IC < 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.
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http://dx.doi.org/10.1038/s41597-022-01532-x | DOI Listing |
Pol J Vet Sci
December 2024
Pasteur Institute of Novi Sad, Hajduk Veljkova 1, 21101 Novi Sad, Serbia.
Constant antigenic changes, new variants and easy transmission of SARS-CoV-2 virus should acquire greater zoonotic attention and need to remain alert. In this retrospective study the aim was to analyze seropositivity to SARS-CoV-2 in dogs by commercial ELISA. The Virus neutralization test (VNT) was modified for the purpose of confirmation of SARS-CoV-2 antibodies in ELISA-positive dog sera.
View Article and Find Full Text PDFAccess Microbiol
September 2024
Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, UK.
The coronavirus 2019 pandemic has highlighted the importance of physiologically relevant models to assist preclinical research. Here, we describe the adaptation of a human alveolus microphysiological system (MPS) model consisting of primary human alveolar epithelial and lung microvascular endothelial cells to study infection with SARS-CoV-2 at Biosafety Level 3 facility. This infection model recapitulates breathing-like stretch and culture of epithelial cells at the air-liquid interface and resulted in clinically relevant cytopathic effects including cell rounding of alveolar type 2 cells and disruption of the tight junction protein occludin.
View Article and Find Full Text PDFJ Invest Dermatol
December 2024
Temerty Faculty of Medicine, University of Toronto, Toronto, Canada; Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Canada; Division of Dermatology, Women's College Hospital, Toronto, Canada. Electronic address:
COVID-19 skin manifestations are multifaceted, ranging from urticaria, morbilliform or papulovesicular rash, livedoid purpuric lesions, and to pseudochilblains (also called COVID toes). Recent insights into the mechanism of these manifestations have highlighted that morbilliform, papulovesicular, and livedoid/purpuric rashes are related to virus-induced endothelial cell damage and linked to moderate-to-severe disease, whereas pseudochilblains are related to an exaggerated IFN-1 production by plasmacytoid dendritic cells in protected individuals. In this paper, we will review the clinical and physiopathological features of cutaneous COVID-19 manifestations in relation to the direct viral cytopathic effects and dysregulated IFN-1 responses.
View Article and Find Full Text PDFJ Dairy Res
December 2024
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Saitama, Japan.
The continuing emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be ameliorated by infection prevention through daily diet. In this study, we examined the anti-SARS-CoV-2 activity of 10 commercially available dairy products. They did not show any cytotoxicity against VeroE6/transmembrane protease serine 2 (TMPRSS2) cells (CC > 4 mg/ml).
View Article and Find Full Text PDFVet Microbiol
January 2025
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China; Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Daqing 163319, China; Engineering Research Center of Prevention and Control of Cattle Diseases, Daqing, Heilongjiang Province 163319, China. Electronic address:
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