Methylene blue is a potent and broad-spectrum inhibitor against Zika virus in vitro and in vivo
| Autor: | Hongmin Li, Cheri A. Koetzner, Zhong Li, Menghang Xia, Anil Mathew Tharappel, Laura D. Kramer, Nicole Trudeau, Lili Kuo, Lianna D'Brant, Saiyang Hu, Subodh Kumar Samrat, David Butler, Yuekun Lang, Natasha Rugenstein, Jing Zhang, Srilatha Sakamuru, Ruili Huang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Epidemiology viruses 030106 microbiology Immunology Biology Dengue virus medicine.disease_cause Microbiology Virus Zika virus 03 medical and health sciences Virology Drug Discovery medicine Protease inhibitor (pharmacology) NS3 Yellow fever virus diseases General Medicine Japanese encephalitis medicine.disease biology.organism_classification Flavivirus 030104 developmental biology Infectious Diseases Parasitology |
| Zdroj: | Emerging Microbes & Infections. 9:2404-2416 |
| ISSN: | 2222-1751 |
| DOI: | 10.1080/22221751.2020.1838954 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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