SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which was rapidly declared a pandemic by the World Health Organization (WHO). Early clinical symptomatology focused mainly on respiratory illnesses. However, a variety of n...

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Published inPLoS biology Vol. 20; no. 11
Main Authors Pinar Mesci, Janaina S. de Souza, Laura Martin-Sancho, Angela Macia, Aurian Saleh, Xin Yin, Cedric Snethlage, Jason W. Adams, Simoni H. Avansini, Roberto H. Herai, Angels Almenar-Queralt, Yuan Pu, Ryan A. Szeto, Gabriela Goldberg, Patrick T. Bruck, Fabio Papes, Sumit K. Chanda, Alysson R. Muotri
Format Journal Article
LanguageEnglish
Published Public Library of Science (PLoS) 01.11.2022
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Summary:The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which was rapidly declared a pandemic by the World Health Organization (WHO). Early clinical symptomatology focused mainly on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are now well-documented. To experimentally determine whether SARS-CoV-2 could replicate in and affect human brain cells, we infected iPSC-derived human brain organoids. Here, we show that SARS-CoV-2 can productively replicate and promote death of neural cells, including cortical neurons. This phenotype was accompanied by loss of excitatory synapses in neurons. Notably, we found that the U.S. Food and Drug Administration (FDA)-approved antiviral Sofosbuvir was able to inhibit SARS-CoV-2 replication and rescued these neuronal alterations in infected brain organoids. Given the urgent need for readily available antivirals, these results provide a cellular basis supporting repurposed antivirals as a strategic treatment to alleviate neurocytological defects that may underlie COVID-19- related neurological symptoms. This study shows that SARS-CoV-2 virus can infect human brain cortical organoids, inducing cell death and synapse loss; application of Sofosbuvir, an FDA-approved antiviral, rescues these neuronal alterations in infected brain organoids.
ISSN:1544-9173
1545-7885