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Sofosbuvir protects human brain organoids against SARS-CoV-2

Pinar MesciiD, Ángela MaciaiD, Aurian Saleh, Laura Martin‐SanchoiD, Xin YiniD, Cedric E. SnethlageiD, Simoni Helena AvansiniiD, Sumit K. ChandaiD, Alysson Renato MuotriiD

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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 SummarySARS-CoV-2 infection causes neuronal death and impaired synaptogenesis, both rescued by Sofosbuvir treatment.

Abstract summary

Claude Opus 5.5 · xhigh effort · 18 Oct 2026 · from the abstract

SARS-CoV-2 infects and kills neural cells in iPSC-derived human brain organoids and impairs synaptogenesis; the approved antiviral sofosbuvir is reported to reverse both effects.

Neurological symptoms were being reported in adults and newborns with COVID-19 while early clinical care concentrated on respiratory illness, leaving open whether SARS-CoV-2 reaches human brain cells at all. An organoid model that shows neural infection and responds to an already-approved antiviral gives a starting point for treating those symptoms.

Key results

  1. SuggestedSARS-CoV-2 infected iPSC-derived human brain organoids and killed neural cells, cortical neurons among them.

    Reported from direct infection of the organoids; the abstract gives no viral titres, infected-cell fractions or death rates, and no comparison condition is quantified. · Abstract

  2. SuggestedInfection was accompanied by impaired synaptogenesis in the organoids.

    Described as a phenotype accompanying neural cell death; no synapse counts, imaging measurements or statistics are given in the abstract. · Abstract

  3. SuggestedTreatment with sofosbuvir, an antiviral already approved by the FDA, rescued both the cell death and the synaptogenesis defect.

    Stated as a rescue in the same organoid system; dose, timing of treatment and the size of the rescue are not reported in the abstract. · Abstract

Methods, data and reproducibility

Human brain organoids derived from induced pluripotent stem cells were infected with SARS-CoV-2, then examined for neural cell death, cortical neuron loss and synaptogenesis, with sofosbuvir tested as a treatment.

  • iPSC-derived human brain organoids infected with SARS-CoV-2 · human
Methods & tools
iPSC-derived human brain organoids, SARS-CoV-2, Sofosbuvir
Limitations (2)
  • Everything rests on an in vitro organoid model; the abstract reports no animal or patient data, and no evidence that sofosbuvir reaches the brain at an effective concentration in people. · noted in this summary
  • No quantification is given for infection, neuronal death, synaptogenesis or the drug rescue, and no drug dose is stated, so effect sizes and the therapeutic window cannot be judged. · noted in this summary

Read this if you use brain organoids to study viral neurotropism, or are weighing repurposed antivirals against the neurological side of COVID-19.

Citations
66

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