Researchers use brain organoids to show how SARS-CoV-2 virus infects cortical neurons

Using human brain organoids, an international team of researchers, led by scientists from the University of California San Diego School of Medicine and the Sanford Consortium, showed how the SARS-CoV-2 virus, responsible for the COVID-19 disease, infects cortical neurons and in particular destroys their synapses, that is, the connections between brain cells that allow them to communicate with each other.

The results, published in the November 3, 2022 issue of the journal PLOS biologythey also report that the antiviral drug sofosbuvir, already approved for the treatment of hepatitis C, effectively inhibits the replication of SARS-CoV-2 and reverses neuronal changes in infected brain organoids.

Emerging vaccines and treatments have reduced the health consequences of COVID-19 in most patients. But the COVID Long phenomenon, characterized by persistent symptoms including neurological deterioration, remains poorly understood and without specific treatment.

This work helps explain some of the neurological symptoms of COVID-19 and, more importantly, suggests that an FDA-approved antiviral drug could be repackaged to restore the health of infected brain cells and treat the long-term neurological consequences of COVID-19. “

Alysson R. Muotri, PhD, lead author of the study, professor in the departments of pediatrics and cellular and molecular medicine at UC San Diego School of Medicine.

Although primarily considered a respiratory disease, COVID-19 can cause temporary or long-lasting neurological symptoms in some patients, ranging from loss of taste and smell, concentration problems (brain fog), and psychological effects such as depression, stroke. , epilepsy and encephalopathy (a change in the function or structure of the brain).

With increasing evidence that the SARS-CoV-2 virus can infect and damage brain cells (including in developing fetuses), the research team has focused on using organoids, self-organizing three-dimensional cells of tissues derived from cultured stem cells that can mimic certain organic functions.

The researchers exposed brain organoids to SARS-CoV-2, observed viral infection and replication, and noted that the virus rapidly reduced the number of excitatory synapses in neurons within seven days of infection. Excitatory synapses increase a neuron’s action potential, while their counterparts, called inhibitory synapses, reduce this potential.

However, when infected organoids were treated with sofosbuvir, viral replication was inhibited and the observed neurological changes were corrected or restored. These findings echo previous computer models that suggested sofosbuvir could be a treatment, as well as previous research by Muotri and colleagues, which showed that sofosbuvir effectively protected and saved neural cells infected with the Zika virus.

“The bottom line is that sofosbuvir appears to be able to stop or prevent the development of neurological symptoms in patients with COVID-19 disease,” Muotri said. “And since it has been shown to pose no safety concerns in pregnant women, it could also be an option to prevent the transmission of SARS-CoV-2 to their unborn babies.

“Obviously, more studies and clinical trials are needed, but these results offer a way forward for the treatment of a disease (the long-standing COVID) that has so far prevented the healing of millions of people around the world.”