Identification of a Novel Inhibitor of Human Rhinovirus Replication and Inflammation in Airway Epithelial Cells

American Journal of Respiratory Cell and Molecular Biology
Zhonghui YangLoretta G Que

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, and the related metabolite S-nitrosoglutathione, are produced in the airway epithelium via nitric oxide synthase (NOS) 2 and have been shown to function in host defense against RV infection. We hypothesized that inhibitors of the S-nitrosoglutathione-metabolizing enzyme, S-nitrosoglutathione 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 proinflammatory and antiviral mediators (e.g., RANTES [regulated upon activation, normal T cell expressed and secreted], CXCL10, and Mx1), and increased Nrf2 (nuclear factor erythroid 2-related factor 2)-dependent genes (e.g., SQSTM1 and TrxR1). In contrast, C3m had no effect on influenza virus H1N1pr8 replicat...Continue Reading

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Citations

Apr 28, 2020·American Journal of Respiratory and Critical Care Medicine·Sejal SaglaniAdnan Custovic
Nov 28, 2020·Microbial Cell Factories·Taha BaghbaniHamed Haddad Kashani
Jul 20, 2021·Journal of Experimental Pharmacology·James A CoultasSebastian L Johnston

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Methods Mentioned

BETA
ELISA
reverse transcription RT-PCR

Software Mentioned

GraphPad
Prism

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