Quinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival

• Type of Material: Article
• Authors: Juan A De la Cruz, Centers for Disease Control and Prevention, Atlanta; Thota Ganesh, Emory University; Becky Diebold, Emory University; Weiping Cao, Centers for Disease Control and Prevention, Atlanta; Amelia Hofstetter, Centers for Disease Control and Prevention, Atlanta; Neetu Singh, Centers for Disease Control and Prevention, Atlanta; Amrita Kumar, Centers for Disease Control and Prevention, Atlanta; James McCoy, Emory University; Priya Ranjan, Centers for Disease Control and Prevention, Atlanta; Susan ME Smith, Emory University; Suryaprakash Sambhara, Centers for Disease Control and Prevention, Atlanta; John Lambeth, Emory University; Shivaprakash Gangappa, Emory University
• Language: English
• Date: 2021-07-19
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Universal : Public Domain Dedication
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0254632
• Title of Journal or Parent Work: PLOS ONE
• Volume: 16
• Issue: 7
• Start Page: e0254632
• End Page: e0254632
• Grant/Funding Information: This study was supported by CDC intramural funding.
• Keywords: MONOCYTES; EXPRESSION; Science & Technology - Other Topics; NADPH OXIDASE; APOPTOSIS; Multidisciplinary Sciences; PROTEIN; AIRWAY; Science & Technology; ROS; MECHANISM; DIFFERENTIATION; INFECTION

Abstract

Superoxide radicals and other reactive oxygen species (ROS) are implicated in influenza A virus-induced inflammation. In this in vitro study, we evaluated the effects of TG6-44, a novel quinazolin-derived myeloperoxidase-specific ROS inhibitor, on influenza A virus (A/ X31) infection using THP-1 lung monocytic cells and freshly isolated peripheral blood mononuclear cells (PBMC). TG6-44 significantly decreased A/X31-induced ROS and virus-induced inflammatory mediators in THP-1 cells (IL-6, IFN-γ, MCP-1, TNF-α, MIP-1β) and in human PBMC (IL-6, IL-8, TNF-α, MCP-1). Interestingly, TG6-44-treated THP-1 cells showed a decrease in percent cells expressing viral nucleoprotein, as well as a delay in translocation of viral nucleoprotein into the nucleus. Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. Taken together, our results demonstrate the anti-inflammatory and anti-infective effects of TG6-44.