Targeting spike protein-induced TLR/NET axis by COVID-19 therapeutic NRICM102 ameliorates pulmonary embolism and fibrosis.

The global COVID-19 pandemic remains a critical public health threat, as existing vaccines and drugs appear insufficient to halt the rapid transmission. During an outbreak from May to August 2021 in Taiwan, patients with severe COVID-19 were administered NRICM102, which was a traditional Chinese medicine (TCM) formula developed based on ...
its predecessor NRICM101 approved for treating mild cases. This study aimed to explore the mechanism of NRICM102 in ameliorating severe COVID-19-related embolic and fibrotic pulmonary injury. NRICM102 was found to disrupt spike protein/ACE2 interaction, 3CL protease activity, reduce activation of neutrophils, monocytes and expression of cytokines (TNF-?, IL-1?, IL-6, IL-8), chemokines (MCP-1, MIP-1, RANTES) and proinflammatory receptor (TLR4). NRICM102 also inhibited the spread of virus and progression to embolic and fibrotic pulmonary injury through reducing prothrombotic (vWF, PAI-1, NET) and fibrotic (c-Kit, SCF) factors, and reducing alveolar type I (AT1) and type II (AT2) cell apoptosis. NRICM102 may exhibit its protective capability via regulation of TLRs, JAK/STAT, PI3K/AKT, and NET signaling pathways. The study demonstrates the ability of NRICM102 to ameliorate severe COVID-19-related embolic and fibrotic pulmonary injury in vitro and in vivo and elucidates the underlying mechanisms.
Mesh Terms:
Angiotensin-Converting Enzyme 2, COVID-19 Drug Treatment, Chemokine CCL5, Cytokines, Fibrosis, Humans, Interleukin-6, Interleukin-8, Lung Injury, Pandemics, Phosphatidylinositol 3-Kinases, Plasminogen Activator Inhibitor 1, Proto-Oncogene Proteins c-akt, Pulmonary Embolism, Spike Glycoprotein, Coronavirus, Toll-Like Receptor 4, Tumor Necrosis Factor-alpha, von Willebrand Factor
Pharmacol Res
Date: Oct. 01, 2022
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