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Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide.

Abstract
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.
AuthorsJoshua A Jackman, Vivian V Costa, Soohyun Park, Ana Luiza C V Real, Jae Hyeon Park, Pablo L Cardozo, Abdul Rahim Ferhan, Isabella G Olmo, Thaiane P Moreira, Jordana L Bambirra, Victoria F Queiroz, Celso M Queiroz-Junior, Giselle Foureaux, Danielle G Souza, Fabiola M Ribeiro, Bo Kyeong Yoon, Evelien Wynendaele, Bart De Spiegeleer, Mauro M Teixeira, Nam-Joon Cho
JournalNature materials (Nat Mater) Vol. 17 Issue 11 Pg. 971-977 (11 2018) ISSN: 1476-4660 [Electronic] England
PMID30349030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Peptides
Topics
  • Animals
  • Antiviral Agents (pharmacokinetics, therapeutic use)
  • Brain (metabolism)
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Peptides (pharmacokinetics, therapeutic use)
  • Zika Virus Infection (drug therapy)

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