Methylene blue is a potent and broad-spectrum inhibitor against Zika virus <i>in vitro</i> and <i>in vivo</i>
Zhong Li, Yuekun Lang, Srilatha Sakamuru, Subodh Kumar Samrat, Nicole Trudeau, Lili Kuo, Natasha Rugenstein, Anil Mathew Tharappel, Lianna D’Brant, Cheri A. Koetzner, Saiyang Hu, Jing Zhang, Ruili Huang, Laura D. Kramer, David Butler, Menghang Xia, Hongmin Li
Abstract
. 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.