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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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. |
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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 |
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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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School of Chemical and Biomedical Engineering |
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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 |
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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 |
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2020 |
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https://hdl.handle.net/10356/138822 |
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1681059113602121728 |