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

Joshua 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

doi:10.1038/s41563-018-0194-2

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

Joshua 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Letter › peer-review

80 Citations (Scopus)

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.

Original language	English
Pages (from-to)	971-977
Number of pages	7
Journal	Nature Materials
Volume	17
Issue number	11
DOIs	https://doi.org/10.1038/s41563-018-0194-2
Publication status	Published - Nov 1 2018
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2018, The Author(s), under exclusive licence to Springer Nature Limited.

ASJC Scopus Subject Areas

General Chemistry
General Materials Science
Condensed Matter Physics
Mechanics of Materials
Mechanical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41563-018-0194-2

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Jackman, J. A., Costa, V. V., Park, S., Real, A. L. C. V., Park, J. H., Cardozo, P. L., Ferhan, A. R., Olmo, I. G., Moreira, T. P., Bambirra, J. L., Queiroz, V. F., Queiroz-Junior, C. M., Foureaux, G., Souza, D. G., Ribeiro, F. M., Yoon, B. K., Wynendaele, E., De Spiegeleer, B., Teixeira, M. M., & Cho, N. J. (2018). Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide. Nature Materials, 17(11), 971-977. https://doi.org/10.1038/s41563-018-0194-2

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title = "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–Barr{\'e} 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.",

author = "Jackman, {Joshua A.} and Costa, {Vivian V.} and Soohyun Park and Real, {Ana Luiza C.V.} and Park, {Jae Hyeon} and Cardozo, {Pablo L.} and Ferhan, {Abdul Rahim} and Olmo, {Isabella G.} and Moreira, {Thaiane P.} and Bambirra, {Jordana L.} and Queiroz, {Victoria F.} and Queiroz-Junior, {Celso M.} and Giselle Foureaux and Souza, {Danielle G.} and Ribeiro, {Fabiola M.} and Yoon, {Bo Kyeong} and Evelien Wynendaele and {De Spiegeleer}, Bart and Teixeira, {Mauro M.} and Cho, {Nam Joon}",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2018",

month = nov,

day = "1",

doi = "10.1038/s41563-018-0194-2",

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Jackman, JA, Costa, VV, Park, S, Real, ALCV, Park, JH, Cardozo, PL, Ferhan, AR, Olmo, IG, Moreira, TP, Bambirra, JL, Queiroz, VF, Queiroz-Junior, CM, Foureaux, G, Souza, DG, Ribeiro, FM, Yoon, BK, Wynendaele, E, De Spiegeleer, B, Teixeira, MM & Cho, NJ 2018, 'Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide', Nature Materials, vol. 17, no. 11, pp. 971-977. https://doi.org/10.1038/s41563-018-0194-2

TY - JOUR

T1 - Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide

AU - Jackman, Joshua A.

AU - Costa, Vivian V.

AU - Park, Soohyun

AU - Real, Ana Luiza C.V.

AU - Park, Jae Hyeon

AU - Cardozo, Pablo L.

AU - Ferhan, Abdul Rahim

AU - Olmo, Isabella G.

AU - Moreira, Thaiane P.

AU - Bambirra, Jordana L.

AU - Queiroz, Victoria F.

AU - Queiroz-Junior, Celso M.

AU - Foureaux, Giselle

AU - Souza, Danielle G.

AU - Ribeiro, Fabiola M.

AU - Yoon, Bo Kyeong

AU - Wynendaele, Evelien

AU - De Spiegeleer, Bart

AU - Teixeira, Mauro M.

AU - Cho, Nam Joon

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41563-018-0194-2

DO - 10.1038/s41563-018-0194-2

M3 - Letter

C2 - 30349030

AN - SCOPUS:85055459709

SN - 1476-1122

VL - 17

SP - 971

EP - 977

JO - Nature Materials

JF - Nature Materials

IS - 11

ER -

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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