Lung and colonic organoid systems, which are generated from human pluripotent stems cells, have been used to identify three FDA-approved drugs that are shown to have antiviral activity against SARS-CoV-2. The study, published in Nature, demonstrates that lung and colonic organoids can serve as models for studying SARS-CoV-2 infection and identifying potential COVID-19 therapeutics.
As cases and deaths attributable to COVID-19 continue to increase worldwide, there is an urgent need to create human-relevant models for studying the biology of SARS-CoV-2 and to facilitate drug screening. SARS-CoV-2 primarily infects the respiratory tract, but almost 25% of patients with COVID-19 also have gastrointestinal symptoms, which are associated with worse outcomes.
Shuibing Chen and colleagues used human pluripotent stem cells to develop lung and colonic organoid models that can be used to assess the susceptibility of lung and gut cells to SARS-CoV-2. They find that the organoids — especially alveolar type-II-like lung cells and enterocytes (cells of the intestinal lining) — express the ACE2 receptor, to which SARS-CoV-2 is known to bind, and can be infected with SARS-CoV-2.
The authors then use the organoids to carry out a screen of FDA-approved drugs. They identify three drugs — imatinib, mycophenolic acid and quinacrine dihydrochloride — that inhibit SARS-CoV-2 entry into the organoids. Treatment with these drugs at physiologically relevant levels before or after SARS-CoV-2 infection prevented the infection of both lung and colonic organoids implanted into humanized mice.
The findings represent a resource for drug screening that could be used to identify COVID-19 therapeutic candidates. Four clinical trials have been registered for the use of imatinib to treat patients with COVID-19, for example, and this study provides experimental data to support these trials.
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