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HIF Prolyl Hydroxylase Inhibitors for COVID-19 Treatment: Pros and Cons

Andrey A Poloznikov1, Stepan A Nersisyan1, Dmitry M Hushpulian2,3

  • 1Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.

Frontiers in Pharmacology
|February 15, 2021
PubMed

The review analyzes the potential advantages and problems associated with using HIF prolyl hydroxylase inhibitors as a treatment for COVID-19. HIF prolyl hydroxylase inhibitors are known to boost endogenous erythropoietin (Epo) and activate erythropoiesis by stabilizing and activating the hypoxia inducible factor (HIF). Recombinant Epo treatment has anti-inflammatory and healing properties, and thus, very likely, will be beneficial for moderate to severe cases of COVID-19. However, HIF PHD inhibition may have a significantly broader effect, in addition to stimulating the endogenous Epo production. The analysis of HIF target genes reveals that some HIF-targets, such as furin, could play a negative role with respect to viral entry. On the other hand, HIF prolyl hydroxylase inhibitors counteract ferroptosis, the process recently implicated in vessel damage during the later stages of COVID-19. Therefore, HIF prolyl hydroxylase inhibitors may serve as a promising treatment of COVID-19 complications, but they are unlikely to aid in the prevention of the initial stages of infection.

Keywords:
SARS-CoVadaptaquinhypoxia inducible factorneuradaptroxadustatvadadustat

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