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

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 lead...

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Published in:	Acta pharmacologica Sinica Vol. 41; no. 12; pp. 1539 - 1546
Main Authors:	Serebrovska, Zoya O., Chong, Elisa Y., Serebrovska, Tetiana V., Tumanovska, Lesia V., Xi, Lei
Format:	Journal Article
Language:	English
Published:	Singapore Springer Singapore 01-12-2020 Nature Publishing Group
Subjects:	ACE2 Angiotensin Angiotensin-converting enzyme 2 Animals Antiviral agents Antiviral Agents - pharmacology Biomedical and Life Sciences Biomedicine Coronaviridae Coronaviruses COVID-19 COVID-19 - drug therapy COVID-19 - physiopathology COVID-19 - virology Cytokine Release Syndrome - virology Cytokine storm Cytokines Drug Development Drug Repositioning Drug therapy Gas exchange Humans Hydroxychloroquine Hypoxia Hypoxia - drug therapy Hypoxia - virology Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Hypoxia-inducible factor 1a Immunology Inflammation Internal Medicine Lethality Medical Microbiology Molecular modelling Molecular Targeted Therapy Pandemics Peptidyl-dipeptidase A Pharmacology/Toxicology Public health Respiratory distress syndrome Review Review Article SARS-CoV-2 - isolation & purification SARS-CoV-2 - pathogenicity Serine Severe acute respiratory syndrome coronavirus 2 Vaccine COVID-19 cytokine hypoxia ACE2 hypoxic conditioning HIF-1α
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	1671-4083 1745-7254
DOI:	10.1038/s41401-020-00554-8