A screen of almost 12,000 clinical stage or FDA approved drugs identifies 13 compounds that inhibit replication of SARS-CoV-2 in cultured cells. The findings are published in Nature.
A practical strategy for developing treatments for COVID-19 is the repurposing of drugs that have been approved or are under clinical investigation, as their pharmacological activities and safety profiles have already been established. Sumit Chanda and colleagues describe a large-scale evaluation of nearly 12,000 drugs for their potential to block viral replication. The screen reveals 100 molecules that can inhibit viral replication, of which 13 show particularly promising characteristics—notably, being effective at realistic dose levels. These include an anti-HIV compound called R 82913, a member of a drug family used to treat diabetes (PPAR-γ agonists) named DS-6930, a potential drug for the treatment of osteoporosis (known as ONO 5334) and apilimod, a drug developed to treat autoimmune disorders such as Crohn’s disease. Three of the most potent compounds—including ONO 5334, apilimod and MDL 28170, which has previously been shown to impair Ebola virus infection—were tested for their ability to reduce SARS-CoV-2 replication in cultured lung tissue. ONO 5334, MDL 28170 and apilimod were shown to reduce the number of infected cells by 72%, 65% and 85%, respectively. Apilimod has previously been found to be well-tolerated in humans, with a favourable safety profile at doses in a range likely to have an antiviral effect in patients.
Many of drugs identified in this study have been tested in clinical settings, which could enable accelerated preclinical and clinical evaluation of these drugs for the treatment of patients with COVID-19, the authors conclude.
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