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Sofosbuvir protects human brain organoids against SARS-CoV-2

View ORCID ProfilePinar Mesci, Angela Macia, Aurian Saleh, Laura Martin-Sancho, View ORCID ProfileXin Yin, Cedric Snethlage, Simoni Avansini, Sumit K. Chanda, View ORCID ProfileAlysson Muotri
doi: https://doi.org/10.1101/2020.05.30.125856
Pinar Mesci
1University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children’s Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037
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Angela Macia
1University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children’s Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037
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Aurian Saleh
1University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children’s Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037
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Laura Martin-Sancho
2Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Xin Yin
2Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Cedric Snethlage
1University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children’s Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037
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Simoni Avansini
1University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children’s Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037
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Sumit K. Chanda
2Immunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
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Alysson Muotri
1University of California San Diego, School of Medicine, Department of Pediatrics/Rady Children’s Hospital San Diego, Department of Cellular & Molecular Medicine, La Jolla, CA 92037
3University of California San Diego, Kavli Institute for Brain and Mind, Center for Academic Research and Training in Anthropogeny (CARTA), La Jolla, CA 92093, USA
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  • For correspondence: muotri@ucsd.edu
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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 Summary SARS-CoV-2 infection causes neuronal death and impaired synaptogenesis, both rescued by Sofosbuvir treatment.

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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 31, 2020.
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Sofosbuvir protects human brain organoids against SARS-CoV-2
Pinar Mesci, Angela Macia, Aurian Saleh, Laura Martin-Sancho, Xin Yin, Cedric Snethlage, Simoni Avansini, Sumit K. Chanda, Alysson Muotri
bioRxiv 2020.05.30.125856; doi: https://doi.org/10.1101/2020.05.30.125856
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Sofosbuvir protects human brain organoids against SARS-CoV-2
Pinar Mesci, Angela Macia, Aurian Saleh, Laura Martin-Sancho, Xin Yin, Cedric Snethlage, Simoni Avansini, Sumit K. Chanda, Alysson Muotri
bioRxiv 2020.05.30.125856; doi: https://doi.org/10.1101/2020.05.30.125856

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