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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-11-01
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| Series: | PLoS Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632769/?tool=EBI |
| _version_ | 1797985651347423232 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Pinar Mesci |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T07:21:26Z |
| format | Article |
| id | doaj.art-d270539d16b945478c694db07d712953 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-11T07:21:26Z |
| publishDate | 2022-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-d270539d16b945478c694db07d7129532022-12-22T04:37:36ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-11-012011SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with SofosbuvirPinar MesciJanaina S. de SouzaLaura Martin-SanchoAngela MaciaAurian SalehXin YinCedric SnethlageJason W. AdamsSimoni H. AvansiniRoberto H. HeraiAngels Almenar-QueraltYuan PuRyan A. SzetoGabriela GoldbergPatrick T. BruckFabio PapesSumit K. ChandaAlysson R. MuotriThe 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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632769/?tool=EBI |
| spellingShingle | 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 SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir PLoS Biology |
| title | SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir |
| title_full | SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir |
| title_fullStr | SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir |
| title_full_unstemmed | SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir |
| title_short | SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir |
| title_sort | sars cov 2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with sofosbuvir |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632769/?tool=EBI |
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