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Sofosbuvir protects human brain organoids against SARS-CoV-2

By Pinar Mesci, Angela Macia, Aurian Saleh, Laura Martin-Sancho, Xin Yin, Cedric Snethlage, Simoni Avansini, Sumit K. Chanda, Alysson R. Muotri

Posted 31 May 2020
bioRxiv DOI: 10.1101/2020.05.30.125856

COVID-19 was rapidly declared a pandemic by the World Health Organization, only three months after the initial outbreak in Wuhan, China. Early clinical care mainly focused on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are also emerging. To determine whether SARS-CoV-2 could target the human brain, we infected iPSC-derived human brain organoids. Our findings show that SARS-CoV-2 was able to infect and kill neural cells, including cortical neurons. This phenotype was accompanied by impaired synaptogenesis. Finally, Sofosbuvir, an FDA-approved antiviral drug, was able to rescue these alterations. Given that there are currently no vaccine or antiviral treatments available, urgent therapies are needed. Our findings put Sofosbuvir forward as potential treatments to alleviate COVID-19-related neurological symptoms. ### Competing Interest Statement Dr. Muotri is a co-founder and has an equity interest in TISMOO, a company dedicated to genetic analysis and human brain organogenesis focusing on therapeutic applications customized for the disorder autism spectrum and other neurological disorders origin genetics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, following its conflict of interest policies.

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