Identification of a Novel Inhibitor of HRV Replication and Inflammation in Airway Epithelial Cells.

Identification of a Novel Inhibitor of HRV Replication and Inflammation in Airway Epithelial Cells. Am J Respir Cell Mol Biol. 2018 Aug 29;: Authors: Yang Z, Bochkov YA, Voelker DR, Foster MW, Que LG Abstract Human rhinovirus (RV), the major cause of the common cold, triggers the majority of acute airway exacerbations in patients with asthma and chronic obstructive pulmonary disease. Nitric oxide (NO), and the related metabolite S-nitrosoglutathione (GSNO), are produced in the airway epithelium via nitric oxide synthase 2 (NOS2) and have been shown to function in host defense against RV infection. We hypothesized that inhibitors of the GSNO-metabolizing enzyme, GSNO reductase (GSNOR), might potentiate the antiviral properties of airway-derived NOS2. Using in vitro models of RV-A serotype 16 (RV-A16) and mNeonGreen-H1N1pr8 infection of human airway epithelial cells, we found that treatment with a previously-characterized GSNOR inhibitor (4-[[2-[[(3-cyanophenyl)methyl]thio]-4-oxothieno-[3,2-d]pyrimidin-3(4H)-yl]methyl]-benzoic acid; referred to as C3m) decreased RV-A16 replication and expression of downstream pro-inflammatory and antiviral mediators (e.g. RANTES, CXCL10 and Mx1), and increased nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent genes (e.g. SQSTM1 and TrxR1). In contrast, C3m had no effect on influenza virus H1N1pr8 replication. Moreover, a structurally dissimilar GSNOR inhibitor (N6022) did not alter RV replic...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research