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bioRxiv · 10.1101/2020.05.30.125856

Sofosbuvir protects human brain organoids against SARS-CoV-2

Mesci, P.·Macia, A.·Saleh, A.·Martin-Sancho, L.·YIN, X.·Snethlage, C.·Avansini, S.·Chanda, S.·Muotri, A.
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Abstract

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 a potential treatment to alleviate COVID-19-related neurological symptoms. One Sentence SummarySARS-CoV-2 infection causes neuronal death and impaired synaptogenesis, both rescued by Sofosbuvir treatment.

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Mesci, P., Macia, A., Saleh, A., Martin-Sancho, L., YIN, X., Snethlage, C., Avansini, S., Chanda, S., Muotri, A.. 2020-05-31. Sofosbuvir protects human brain organoids against SARS-CoV-2. https://doi.org/10.1101/2020.05.30.125856

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