By Sola Ogundipe
A team led by scientists in the Perelman School of Medicine at the University of Pennsylvania have identified nine potential new COVID-19 treatments, including three that are already approved by the Food and Drug Administration (FDA) for treating other diseases.
The team, whose findings are published in Cell Reports, screened thousands of existing drugs and drug-like molecules for the ability to inhibit the replication of the COVID-19 virus.
Of the nine drugs found to reduce the replication in respiratory cells, three already have FDA approval
“Our discoveries here suggest new avenues for therapeutic interventions against COVID-19, and also underscore the importance of testing candidate drugs in respiratory cells,” said Dr Sara Cherry, a professor of Pathology and Laboratory Medicine and scientific director of the High-Throughput Screening (HTS) Core at Penn Medicine.
Although great progress has been made in the development of vaccines and treatments for the SARS-CoV-2 coronavirus, there is still much room for improvement.
For their screening project, Cherry and colleagues assembled a library of 3,059 compounds, including about 1,000 FDA-approved drugs and more than 2,000 drug-like molecules that have shown activity against defined biological targets. They then tested all for their ability to significantly inhibit replication in infected cells, without causing much toxicity.
They identified a suitable cell line, Calu-3, that is derived from human airway-lining cells. They used these respiratory-derived cells to test the antiviral compounds identified through the human liver cell screen and found that only nine had activity in the new cells.
By identifying different sets of drugs that work in different cell types, the researchers also shed light on the mechanisms the coronavirus uses to gain entry to cells.
The nine antivirals active in respiratory cells did include salinomycin, a veterinary antibiotic that is also being investigated as an anticancer drug; the kinase enzyme inhibitor dacomitinib, an anticancer drug; bemcentinib, another kinase inhibitor now being tested against cancers; the antihistamine drug ebastine; and cyclosporine, an immune-suppressing drug commonly used to prevent the immune rejection of transplanted organs.
The study highlights cyclosporine as particularly promising, as it appears to works against SARS-CoV-2 in respiratory and non-respiratory cells, and via two distinct mechanisms: inhibiting cell enzymes called cyclophilins, which the coronavirus hijacks to support itself, and suppressing the potentially lethal inflammation of severe COVID-19.
“There may be important benefits to the use of cyclosporine in hospitalized COVID-19 patients, and ongoing clinical trials at Penn and elsewhere are testing that hypothesis,” Cherry said.