@article {1589757,
	title = {Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute Respiratory Syndrome Coronavirus 2 Host Mediators},
	journal = {Am J Pathol},
	volume = {191},
	number = {7},
	year = {2021},
	month = {2021 07},
	pages = {1193-1208},
	abstract = {Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-β1 and tumor necrosis factor-α, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in\&nbsp;vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.},
	keywords = {Angiotensin-Converting Enzyme 2, Animals, Bleomycin, Cells, Cultured, Core Binding Factor Alpha 2 Subunit, COVID-19, Disease Models, Animal, Epithelial Cells, Female, Furin, Lung, Male, Mice, Pulmonary Fibrosis, Treatment Outcome},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2021.04.006},
	author = {O{\textquoteright}Hare, Michael and Amarnani, Dhanesh and Whitmore, Hannah A B and An, Miranda and Marino, Claudia and Ramos, Leslie and Delgado-Tirado, Santiago and Hu, Xinyao and Chmielewska, Natalia and Chandrahas, Anita and Fitzek, Antonia and Heinrich, Fabian and Steurer, Stefan and Ondruschka, Benjamin and Glatzel, Markus and Krasemann, Susanne and Sepulveda-Falla, Diego and Lagares, David and Pedron, Julien and Bushweller, John H and Liu, Paul and Arboleda-Velasquez, Joseph F and Kim, Leo A}
}
