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Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets

   
@article{APS10234,
	author = {Zoya O. Serebrovska and Elisa Y. Chong and Tetiana V. Serebrovska and Lesia V. Tumanovska and Lei Xi},
	title = {Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets},
	journal = {Acta Pharmacologica Sinica},
	volume = {41},
	number = {12},
	year = {2020},
	keywords = {},
	abstract = {The pandemic of coronavirus disease 2019 (COVID-19) and its pathogen, severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) have become the greatest current threat to global public health. The highly infectious SARS-CoV-2 virus primarily attacks pulmonary tissues and impairs gas exchange leading to acute respiratory distress syndrome (ARDS) and systemic hypoxia. The current pharmacotherapies for COVID-19 largely rely on supportive and anti-thrombi treatment and the repurposing of antimalarial and antiviral drugs such as hydroxychloroquine and remdesivir. For a better mechanistic understanding of COVID-19, our present review focuses on its primary pathophysiologic features: hypoxia and cytokine storm, which are a prelude to multiple organ failure and lethality. We discussed a possible link between the activation of hypoxia inducible factor 1α (HIF-1α) and cell entry of SARS- CoV-2, since HIF-1α is shown to suppress the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) and upregulate disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). In addition, the protein targets of HIF-1α are involved with the activation of pro-inflammatory cytokine expression and the subsequent inflammatory process. Furthermore, we hypothesized a potential utility of so-called “hypoxic conditioning” to activate HIF-1α- induced cytoprotective signaling for reduction of illness severity and improvement of vital organ function in patients with COVID- 19. Taken together, we would propose further investigations into the hypoxia-related molecular mechanisms, from which novel targeted therapies can be developed for the improved management of COVID-19.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/10234}
}