Novel Drug Use to Treat and Prevent COVID-19
August 6, 2020
Novel drug use and drug screening system for SARS-CoV-2 therapies.
The outbreak of coronavirus disease COVID-19 caused by the novel SARS-CoV-2 virus has wreaked havoc on communities, economies, and healthcare systems worldwide and has resulted in nearly 400,000 deaths. In addition to causing respiratory dysfunction, in nearly 25% of patients SARS-CoV-2 affects the digestive system; digestive symptoms like diarrhea, vomiting, and abdominal pain are associated with worse outcomes. Few treatment options for COVID-19 exist, and drug development and repurposing efforts are hindered by the limited knowledge of the virus biology and the lack of appropriate disease models. Transgenic animals expressing human ACE2 receptors, which are required for SARS-CoV-2 to enter host cells, serve as the primary disease model but do not fully recapitulate the human cells and tissues.
The inventors conducted an extensive drug screen in a novel human colonic organoid disease model and identified four drug candidates including Mycophenolic acid that block SARS-CoV-2 entry into cells. Viral entry is the earliest stage of the viral infection, as the virus comes into contact with the host cell and infects it with viral material. This invention includes the novel use of these generic drugs for prevention and treatment of COVID-19 and a novel disease model and a drug screening system based on human pluripotent stem cell (hPSC)-derived colonic organoids.
- Treatment and prevention of COVID-19 disease
- Organoid system to study COVID-19 and perform high throughput drug screening
- Repurposing of off-patent generic FDA-approved drug can be quickly and safely validated and deployed to the clinic
- hPSC-derived colon organoids recapitulate relevant organ biology and can be used in-vitro and in-vivo in animal models to study COVID-19 and perform drug screening
- Duan, X. et al. Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids. bioRxiv, published May 02, 2020. doi: https://doi.org/10.1101/2020.05.02.073320
- Shuibing Chen
- Todd Evans
- Xiaochua Duan
- Yuling Han
- Liuliu Yang