Discovery of clinically approved drugs capable of inhibiting SARS-CoV-2 in vitro infection using a phenotypic screening strategy and network-analysis to predict their potential to treat covid-19
Douglas Ferreira Sales-Medina, Ludmila Rodrigues Pinto Ferreira, Lavínia M. D. Romera, Karolina Ribeiro Gonçalves, Rafael V. C. Guido, Gilles Courtemanche, Marcos S. Buckeridge, Édison L. Durigon, Carolina B. Moraes, Lucio H. Freitas-Junior
Abstract
The disease caused by SARS-CoV2, covid-19, rapidly spreads worldwide, causing the
greatest threat to global public health in the last 100 years. This scenario has become
catastrophic as there are no approved vaccines to prevent the disease, and the main
measures to contain the virus transmission are confinement and social distancing. One
priority strategy is based on drug repurposing by pursuing antiviral chemotherapy that
can control transmission and prevent complications associated with covid-19. With this
aim, we performed a high content screening assay for the discovery of anti-SARS-CoV-2
compounds. From the 65 screened compounds, we have found four drugs capable to
selectively inhibit SARS-CoV-2 in vitro infection: brequinar, abiraterone acetate,
neomycin, and the extract of Hedera helix. Brequinar and abiraterone acetate had higher
inhibition potency against SARS-CoV-2 than neomycin and Hedera helix extract,
respectively. Drugs with reported antiviral activity and in clinical trials for covid-19,
chloroquine, ivermectin, and nitazoxanide, were also included in the screening, and the
last two were found to be non-selective. We used a data mining approach to build drughost molecules-biological function-disease networks to show in a holistic way how each
compound is interconnected with host node molecules and virus infection, replication,
inflammatory response, and cell apoptosis. In summary, the present manuscript identified
four drugs with active inhibition effect on SARS-CoV-2 in vitro infection, and by network
analysis, we provided new insights and starting points for the clinical evaluation and
repurposing process to treat SARS-CoV-2 infection.
CORDITE (CORona Drug InTEractions database) collects and aggregates data from PubMed, MedRxiv, BioRxiv, ChemRxiv and PMC for SARS-CoV-2. Its main focus is set on drug interactions either addressing viral proteins or human proteins that could be used to treat COVID.
It collects and provides up-to-date information on computational predictions, in vitro, as well as in vivo study data.
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