Therapeutic potency of compound RMY-205 for pulmonary fibrosis induced by SARS-CoV-2 nucleocapsid protein.
Cell Chem Biol
; 30(3): 261-277.e8, 2023 03 16.
Article
in English
| MEDLINE | ID: covidwho-2288731
ABSTRACT
Pulmonary fibrosis is a typical sequela of coronavirus disease 2019 (COVID-19), which is linked with a poor prognosis for COVID-19 patients. However, the underlying mechanism of pulmonary fibrosis induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here, we demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 induced pulmonary fibrosis by activating pulmonary fibroblasts. N protein interacted with the transforming growth factor ß receptor I (TßRI), to disrupt the interaction of TßRI-FK506 Binding Protein12 (FKBP12), which led to activation of TßRI to phosphorylate Smad3 and boost expression of pro-fibrotic genes and secretion of cytokines to promote pulmonary fibrosis. Furthermore, we identified a compound, RMY-205, that bound to Smad3 to disrupt TßRI-induced Smad3 activation. The therapeutic potential of RMY-205 was strengthened in mouse models of N protein-induced pulmonary fibrosis. This study highlights a signaling pathway of pulmonary fibrosis induced by N protein and demonstrates a novel therapeutic strategy for treating pulmonary fibrosis by a compound targeting Smad3.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pulmonary Fibrosis
/
COVID-19
Type of study:
Prognostic study
Topics:
Long Covid
Limits:
Animals
Language:
English
Journal:
Cell Chem Biol
Year:
2023
Document Type:
Article
Affiliation country:
J.chembiol.2023.02.004
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