Open AccessQuinazolin-derived myeloperoxidase inhibitor suppresses influenza A virus-induced reactive oxygen species, pro-inflammatory mediators and improves cell survival
Author(s) -
Juan A. De La Cruz,
Thota Ganesh,
Becky A. Diebold,
Weiping Cao,
Amelia R. Hofstetter,
Neetu Singh,
Amrita Kumar,
James McCoy,
Priya Ranjan,
Susan Smith,
Suryaprakash Sambhara,
J. David Lambeth,
Shivaprakash Gangappa
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0254632
Subject(s) - myeloperoxidase , reactive oxygen species , peripheral blood mononuclear cell , influenza a virus , virus , biology , apoptosis , inflammation , tumor necrosis factor alpha , microbiology and biotechnology , virology , chemistry , immunology , in vitro , biochemistry
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.