Zika virus is a mosquito-borne virus that is associated with neurodegenerative diseases, including Guillain–Barré syndrome¹ and congenital Zika syndrome². As Zika virus targets the nervous system, there is an urgent need to develop therapeutic strategies that inhibit Zika virus infection in the brain. Here, we have engineered a brain-penetrating peptide that works against Zika virus and other mosquito-borne viruses. We evaluated the therapeutic efficacy of the peptide in a lethal Zika virus mouse model exhibiting systemic and brain infection. Therapeutic treatment protected against mortality and markedly reduced clinical symptoms, viral loads and neuroinflammation, as well as mitigated microgliosis, neurodegeneration and brain damage. In addition to controlling systemic infection, the peptide crossed the blood–brain barrier to reduce viral loads in the brain and protected against Zika-virus-induced blood–brain barrier injury. Our findings demonstrate how engineering strategies can be applied to develop peptide therapeutics and support the potential of a brain-penetrating peptide to treat neurotropic viral infections.

寨卡病毒是由蚊子传播的病毒，与神经退行性疾病（包括格林-巴雷综合征¹和先天性寨卡综合征^2）有关。由于寨卡病毒靶向神经系统，因此迫切需要开发出抑制大脑中寨卡病毒感染的治疗策略。在这里，我们设计了一种可穿透脑的肽，可抵抗寨卡病毒和其他蚊媒病毒。我们评估了在表现出全身性和脑部感染的致命寨卡病毒小鼠模型中该肽的治疗效果。治疗性治疗可防止死亡，并显着减少临床症状，病毒载量和神经炎症，并减轻小胶质细胞增生，神经变性和脑损伤。除控制全身感染外，该肽还穿越血脑屏障以减少大脑中的病毒载量，并防止寨卡病毒引起的血脑屏障损伤。