PLoS Biol—逆转新冠病毒的神经毒性

中文摘要

严重急性呼吸窘迫综合征冠状病毒2型（SARS-CoV-2）是2019年冠状病毒病（新冠肺炎）的病原体，世界卫生组织（WHO）迅速宣布该病处于大流行。早期临床症状研究主要关注呼吸系统疾病。然而，成人和新生儿的各种神经系统表现现在已经得到了重视。为了通过实验确定SARS-CoV-2是否能在人脑细胞中复制并影响人脑细胞，科学家感染了iPSC衍生的人脑类器官。在这里，他们发现SARS-CoV-2可以有效地在神经细胞中复制并诱导皮层神经元的死亡，同时也伴随着神经元兴奋性突触的丢失。值得注意的是，他们发现美国食品和药物管理局（FDA）批准的抗病毒药物Sofosbuvir（索非布韦）能够抑制SARS-CoV-2的复制，并挽救了受感染大脑器官中的这些神经元改变。鉴于迫切需要现成的抗病毒药物，这些结果为该药的使用提供了细胞基础，因此，可将重组抗病毒药物作为战略治疗，以缓解引起新冠肺炎相关神经症状的神经细胞学缺陷。

英文摘要

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.

参考文献：SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir. PLoS Biol. 2022 Nov 3;20(11):e3001845. doi: 10.1371/journal.pbio.3001845. eCollection 2022 Nov.

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