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

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 brai...

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Main Authors: Jackman, Joshua A., Costa, Vivian V., Park, Soohyun, Real, Ana Luiza Campos Vila, Park, Jae Hyeon, Cardozo, Pablo L., Abdul Rahim Ferhan, Olmo, Isabella G., Moreira, Thaiane P., Bambirra, Jordana L., Queiroz, Victoria F., Queiroz-Junior, Celso M., Foureaux, Giselle, Souza, Danielle G., Ribeiro, Fabiola M., Yoon, Bo Kyeong, Wynendaele, Evelien, Spiegeleer, Bart De, Teixeira, Mauro M., Cho, Nam-Joon
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/138822
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1388222020-06-01T10:26:40Z Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide Jackman, Joshua A. Costa, Vivian V. Park, Soohyun Real, Ana Luiza Campos Vila Park, Jae Hyeon Cardozo, Pablo L. Abdul Rahim Ferhan Olmo, Isabella G. Moreira, Thaiane P. Bambirra, Jordana L. Queiroz, Victoria F. Queiroz-Junior, Celso M. Foureaux, Giselle Souza, Danielle G. Ribeiro, Fabiola M. Yoon, Bo Kyeong Wynendaele, Evelien Spiegeleer, Bart De Teixeira, Mauro M. Cho, Nam-Joon School of Chemical and Biomedical Engineering School of Materials Science & Engineering Science::Medicine Antiviral Agents Drug Development 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. NRF (Natl Research Foundation, S’pore) NMRC (Natl Medical Research Council, S’pore) 2020-05-13T03:37:42Z 2020-05-13T03:37:42Z 2018 Journal Article Jackman, J. A., Costa, V. V., Park, S., Real, A. L. C. V., Park, J. H., Cardozo, P. L., . . . Cho, N.-J. (2018). Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide. Nature Materials, 17(11), 971-977. doi:10.1038/s41563-018-0194-2 1476-1122 https://hdl.handle.net/10356/138822 10.1038/s41563-018-0194-2 30349030 2-s2.0-85055459709 11 17 971 977 en Nature Materials © 2018 The Author(s), under exclusive licence to Springer Nature Limited. All rights reserved.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic Science::Medicine
Antiviral Agents
Drug Development
spellingShingle Science::Medicine
Antiviral Agents
Drug Development
Jackman, Joshua A.
Costa, Vivian V.
Park, Soohyun
Real, Ana Luiza Campos Vila
Park, Jae Hyeon
Cardozo, Pablo L.
Abdul Rahim Ferhan
Olmo, Isabella G.
Moreira, Thaiane P.
Bambirra, Jordana L.
Queiroz, Victoria F.
Queiroz-Junior, Celso M.
Foureaux, Giselle
Souza, Danielle G.
Ribeiro, Fabiola M.
Yoon, Bo Kyeong
Wynendaele, Evelien
Spiegeleer, Bart De
Teixeira, Mauro M.
Cho, Nam-Joon
Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide
description 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.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Jackman, Joshua A.
Costa, Vivian V.
Park, Soohyun
Real, Ana Luiza Campos Vila
Park, Jae Hyeon
Cardozo, Pablo L.
Abdul Rahim Ferhan
Olmo, Isabella G.
Moreira, Thaiane P.
Bambirra, Jordana L.
Queiroz, Victoria F.
Queiroz-Junior, Celso M.
Foureaux, Giselle
Souza, Danielle G.
Ribeiro, Fabiola M.
Yoon, Bo Kyeong
Wynendaele, Evelien
Spiegeleer, Bart De
Teixeira, Mauro M.
Cho, Nam-Joon
format Article
author Jackman, Joshua A.
Costa, Vivian V.
Park, Soohyun
Real, Ana Luiza Campos Vila
Park, Jae Hyeon
Cardozo, Pablo L.
Abdul Rahim Ferhan
Olmo, Isabella G.
Moreira, Thaiane P.
Bambirra, Jordana L.
Queiroz, Victoria F.
Queiroz-Junior, Celso M.
Foureaux, Giselle
Souza, Danielle G.
Ribeiro, Fabiola M.
Yoon, Bo Kyeong
Wynendaele, Evelien
Spiegeleer, Bart De
Teixeira, Mauro M.
Cho, Nam-Joon
author_sort Jackman, Joshua A.
title Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide
title_short Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide
title_full Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide
title_fullStr Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide
title_full_unstemmed Therapeutic treatment of Zika virus infection using a brain-penetrating antiviral peptide
title_sort therapeutic treatment of zika virus infection using a brain-penetrating antiviral peptide
publishDate 2020
url https://hdl.handle.net/10356/138822
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