Methylene blue is a potent and broad-spectrum inhibitor against Zika virus in vitro and in vivo
Many flaviviruses including the Dengue virus (DENV), Zika virus (ZIKV), West Nile virus, Yellow Fever virus, and Japanese encephalitis virus are significant human pathogens, unfortunately without any specific therapy. Here, we demonstrate that methylene blue, an FDA-approved drug, is a broad-spectrum and potent antiviral against Zika virus and Dengue virus both in vitro and in vivo. We found that methylene blue can considerably inhibit the interactions between viral protease NS3 and its NS2B co-factor, inhibit viral protease activity, inhibit viral growth, protect 3D mini-brain organoids from ZIKV infection, and reduce viremia in a mouse model. Mechanistic studies confirmed that methylene blue works in both entry and post entry steps, reduces virus production in replicon cells and inhibited production of processed NS3 protein. Overall, we have shown that methylene blue is a potent antiviral for management of flavivirus infections, particularly for Zika virus. As an FDA-approved drug, methylene blue is well-tolerated for human use. Therefore, methylene blue represents a promising and easily developed therapy for management of infections by ZIKV and other flaviviruses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Emerging microbes & infections - 9(2020), 1 vom: 04. Dez., Seite 2404-2416 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Zhong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.06.2021 Date Revised 02.06.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/22221751.2020.1838954 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316480045 |
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| 100 | 1 | |a Li, Zhong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Methylene blue is a potent and broad-spectrum inhibitor against Zika virus in vitro and in vivo |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 02.06.2021 | ||
| 500 | |a Date Revised 02.06.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Many flaviviruses including the Dengue virus (DENV), Zika virus (ZIKV), West Nile virus, Yellow Fever virus, and Japanese encephalitis virus are significant human pathogens, unfortunately without any specific therapy. Here, we demonstrate that methylene blue, an FDA-approved drug, is a broad-spectrum and potent antiviral against Zika virus and Dengue virus both in vitro and in vivo. We found that methylene blue can considerably inhibit the interactions between viral protease NS3 and its NS2B co-factor, inhibit viral protease activity, inhibit viral growth, protect 3D mini-brain organoids from ZIKV infection, and reduce viremia in a mouse model. Mechanistic studies confirmed that methylene blue works in both entry and post entry steps, reduces virus production in replicon cells and inhibited production of processed NS3 protein. Overall, we have shown that methylene blue is a potent antiviral for management of flavivirus infections, particularly for Zika virus. As an FDA-approved drug, methylene blue is well-tolerated for human use. Therefore, methylene blue represents a promising and easily developed therapy for management of infections by ZIKV and other flaviviruses | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dengue virus | |
| 650 | 4 | |a Methylene blue | |
| 650 | 4 | |a Zika virus | |
| 650 | 4 | |a antiviral | |
| 650 | 4 | |a flavivirus | |
| 650 | 4 | |a protease inhibitor | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a NS2B protein, flavivirus |2 NLM | |
| 650 | 7 | |a NS3 protein, flavivirus |2 NLM | |
| 650 | 7 | |a Protease Inhibitors |2 NLM | |
| 650 | 7 | |a Viral Nonstructural Proteins |2 NLM | |
| 650 | 7 | |a Viral Proteins |2 NLM | |
| 650 | 7 | |a NS3 protein, zika virus |2 NLM | |
| 650 | 7 | |a EC 3.4.- |2 NLM | |
| 650 | 7 | |a Serine Endopeptidases |2 NLM | |
| 650 | 7 | |a EC 3.4.21.- |2 NLM | |
| 650 | 7 | |a RNA Helicases |2 NLM | |
| 650 | 7 | |a EC 3.6.4.13 |2 NLM | |
| 650 | 7 | |a Methylene Blue |2 NLM | |
| 650 | 7 | |a T42P99266K |2 NLM | |
| 700 | 1 | |a Lang, Yuekun |e verfasserin |4 aut | |
| 700 | 1 | |a Sakamuru, Srilatha |e verfasserin |4 aut | |
| 700 | 1 | |a Samrat, Subodh |e verfasserin |4 aut | |
| 700 | 1 | |a Trudeau, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Kuo, Lili |e verfasserin |4 aut | |
| 700 | 1 | |a Rugenstein, Natasha |e verfasserin |4 aut | |
| 700 | 1 | |a Tharappel, Anil |e verfasserin |4 aut | |
| 700 | 1 | |a D'Brant, Lianna |e verfasserin |4 aut | |
| 700 | 1 | |a Koetzner, Cheri A |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Saiyang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ruili |e verfasserin |4 aut | |
| 700 | 1 | |a Kramer, Laura D |e verfasserin |4 aut | |
| 700 | 1 | |a Butler, David |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Menghang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hongmin |e verfasserin |4 aut | |
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