The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice

Viruses

Michael V. Callahan¹  Kelly L. Warfield²  Aruna Sampath²  Mansoora Khaliq²  Donald F. Smee³  Craig W. Day³  Dale L. Barnard³  Sven G. Enterlein⁴  Urban Ramstedt⁵ 

[1] Division of Infectious Diseases, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA;Emergent BioSolutions, Gaithersburg, MD 20879, USA;Institute for Antiviral Research, Utah State University, Logan, UT 84322-5600, USA;Integrated Biotherapeutics Inc., Gaithersburg, MD 20878, USA;Unither Virology, LLC, Silver Spring, MD 20910, USA;

关键词: Iminosugar;    UV-4B;    influenza;    human bronchial epithelial cells;    antiviral;    mice;   

DOI  :  10.3390/v8030071

来源: DOAJ

【 摘 要 】

Iminosugars that are competitive inhibitors of endoplasmic reticulum (ER) α-glucosidases have been demonstrated to have antiviral activity against a diverse set of viruses. A novel iminosugar, UV-4B, has recently been shown to provide protection against lethal infections with dengue and influenza A (H1N1) viruses in mice. In the current study, the breadth of activity of UV-4B against influenza was examined ex vivo and in vivo. Efficacy of UV-4B against influenza A and B viruses was shown in primary human bronchial epithelial cells, a principal target tissue for influenza. Efficacy of UV-4B against influenza A (H1N1 and H3N2 subtypes) and influenza B was demonstrated using multiple lethal mouse models with readouts including mortality and weight loss. Clinical trials are ongoing to demonstrate safety of UV-4B and future studies to evaluate antiviral activity against influenza in humans are planned.

【 授权许可】

Unknown