Methylene blue is a potent and broad-spectrum inhibitor against Zika virus in vitro and in vivo

Zhong Li, Yuekun Lang, Srilatha Sakamuru, Subodh Samrat, Nicole Trudeau, Lili Kuo, Natasha Rugenstein, Anil Tharappel, Lianna D'Brant, Cheri A. Koetzner, Saiyang Hu, Jing Zhang, Ruili Huang, Laura D. Kramer, David Butler, Menghang Xia, Hongmin Li

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2404-2416
Number of pages13
JournalEmerging Microbes and Infections
Issue number1
StatePublished - Jan 1 2020
Externally publishedYes


  • Dengue virus
  • Methylene blue
  • Zika virus
  • antiviral
  • flavivirus
  • protease inhibitor

ASJC Scopus subject areas

  • Drug Discovery
  • Infectious Diseases
  • Epidemiology
  • Virology
  • Parasitology
  • Microbiology
  • Immunology


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