Using human brain organoids, an international team of researchers led by scientists at UC San Diego School of Medicine and the Sanford Consortium has demonstrated how the SARS-CoV-2 virus that causes COVID-19 infects cortical neurons and specifically destroys their Synapses – The connections between brain cells that allow them to communicate with each other.
The findings were published on November 3, 2022 PLoS Biologyalso reported that the antiviral drug sofosbuvir, already approved for the treatment of hepatitis C, effectively inhibited SARS-CoV-2 replication and reversed neuronal changes in infected brain organoids.
“Vaccines and emerging therapies have reduced the health effects of COVID-19 for most patients,” said senior study author Dr. Alysson R. Muotri, professor in the Departments of Pediatrics and Cell and Molecules at the UC San Diego School of Medicine. “However, the long-term COVID phenomenon characterized by persistent symptoms including neurological dysfunction remains poorly understood and without any specific remedy.
“This work helps explain some of the neurological symptoms of COVID-19 and, more importantly, it suggests that FDA-approved antiviral drugs may be repurposed to restore infected brain cells to health and address the long-term effects of COVID-19 Nervous system consequences.”
Although primarily considered a respiratory illness, COVID-19 may cause some patients to experience temporary or long-term neurological symptoms, including loss of taste and smell, difficulty concentrating (brain fog), as well as depression, stroke, seizures, etc. Psychological effects and encephalopathy (changes in brain function or structure).
With mounting evidence that the SARS-CoV-2 virus can infect and alter brain cells, including the developing fetus, the team focused on using organoids—self-organizing three-dimensional tissues derived from cultured stem cells that can Mimic some organ functions.
The researchers exposed brain organoids to SARS-CoV-2 and observed viral infection and replication, noting that the virus rapidly reduced the number of excitatory synapses in neurons within seven days of infection. Excitatory synapses increase the firing action potential of neurons, while their counterparts, called inhibitory synapses, decrease this potential.
However, when infected organoids were treated with sofosbuvir, viral replication was inhibited and neuronal damage was observed to be rescued or restored. The findings echo earlier computational modeling that suggested sofosbuvir could be a treatment, and previous research by Muotri and colleagues that found sofosbuvir effectively protected and rescued Zika-infected nerve cells .
“Most importantly, sofosbuvir appears to have the potential to prevent or prevent neurological symptoms in COVID-19 patients,” Muotri said. “And since it has been shown to have no safety concerns for pregnant women, it may also be an option to prevent the spread of SARS-CoV-2 to unborn children.
“Further research and clinical trials are needed, of course, but these findings offer a way forward for treating a disease that has so far held back millions of people around the world (long-term COVID).”
Co-authors include: Pinar Mesci, Janaina S. de Souza, Angela Macia, Aurian Saleh, Cedric Snethlage, Jason W. Adams, Angels Almenar-Queralt, Ryan A. Szeto, Gabriela Goldberg, and Patrick T. Bruck, all from UC San Francisco UC San Diego and Lady Children’s Hospital – San Diego; Laura Martin-Sancho, Yuan Pu and Sumit K. Chandra, Sanford Burnham Prebys Medical Discovery Institute; Simoni H. Avansini and Fabio Papes, UC San Diego and University of Campinas, Brazil and Roberto H. Herai, Pontificia Universidade Catolica do Parana, Brazil and Lico Kaesemodel Institute, Brazil.