The study, published in the journal Cell Reports, looked at thousands of existing drugs and drug-like molecules for their ability to inhibit replication of the coronavirus that causes Covid-19, SARS-CoV-2.
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Of the nine drugs that reduce the replication of SARS-CoV-2 in respiratory cells, three already have FDA approval – the transplant rejection drug, cyclosporine, the cancer drug dacomitinib and the antibiotic salinomycin.
“Our findings here suggest new avenues for therapeutic interventions against Covid-19 and also highlight the importance of testing candidate drugs in respiratory cells,” said researcher Sara Cherry, from the University of Pennsylvania.
For the study, the researchers assembled a library of 3,059 compounds, including about 1,000 FDA approved drugs and more than 2,000 drug-like molecules that showed activity against defined biological targets.
They then tested all of them for their ability to significantly inhibit SARS-CoV-2 replication in infected cells, without causing too much toxicity.
Initially, they performed antiviral screens using cell types that could easily grow in the laboratory and infect with SARS-CoV-2, that is, African green monkey kidney cells and a cell line derived from human liver cells.
With these screens, they identified and validated several compounds that functioned in monkey kidney cells and 23 that functioned in human liver cells. Hydroxychloroquine, used as a medicine against malaria, and remdesivir were effective in both types of cells.
Because SARS-CoV-2 is primarily a respiratory virus and is believed to initiate infections via airway lining cells, the researchers looked for a type of respiratory cell that could experimentally infect the virus.
They finally identified a suitable cell line, Calu-3, which is derived from human cells in the lining of the airways.
They used these cells derived from the respiratory system to test the antiviral compounds identified by screening human liver cells and found that only nine had activity on the new cells. The nine did not include hydroxychloroquine.
The nine antivirals active in respiratory cells include salinomycin, a veterinary antibiotic that is also being investigated as an anticancer drug; the enzyme kinase inhibitor dacomitinib, an anti-cancer drug; bemcentinib, another kinase inhibitor now tested against cancer; the antihistamine drug ebastine; and cyclosporine, an immunity-suppressing drug commonly used to prevent immune rejection of transplanted organs.
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