Title:NOX-2 Inhibitors may be Potential Drug Candidates for the Management
of COVID-19 Complications
Volume: 16
Issue: 2
Author(s): Bimalendu Chowdhury*, Biswa Mohan Sahoo, Akankshya Priyadarsani Jena, Korikana Hiramani, Amulyaratna Behera and Biswajeet Acharya
Affiliation:
- Department of Pharmacology, Roland Institute of Pharmaceutical Sciences, Khodasingi, Berhampur, 760010, Odisha,
India
Keywords:
NADPH-oxidase, NOX-2, pulmonary fibrosis, RNA virus, platelet aggregation, ROS.
Abstract: COVID-19 is an RNA virus that attacks the targeting organs, which express angiotensin-
converting enzyme-2 (ACE-2), such as the lungs, heart, renal system, and gastrointestinal
tract. The virus that enters the cell by endocytosis triggers ROS production within the confines of
endosomes via a NOX-2 containing NADPH-oxidase. Various isoforms of NADPH oxidase are
expressed in airways and alveolar epithelial cells, endothelial and vascular smooth muscle cells,
and inflammatory cells, such as alveolar macrophages, monocytes, neutrophils, and Tlymphocytes.
The key NOX isoform expressed in macrophages and neutrophils is the NOX-2 oxidase,
whereas, in airways and alveolar epithelial cells, it appears to be NOX-1 and NOX-2. The
respiratory RNA viruses induce NOX-2-mediated ROS production in the endosomes of alveolar
macrophages. The mitochondrial and NADPH oxidase (NOX) generated ROS can enhance TGF-β
signaling to promote fibrosis of the lungs. The endothelium-derived ROS and platelet-derived
ROS, due to activation of the NADPH-oxidase enzyme, play a crucial role in platelet activation. It
has been observed that NOX-2 is generally activated in COVID-19 patients. The post-COVID
complications like pulmonary fibrosis and platelet aggregation may be due to the activation of
NOX-2. NOX-2 inhibitors may be a useful drug candidate to prevent COVID-19 complications
like pulmonary fibrosis and platelet aggregation.