Frontiers in Pharmacology (Jan 2021)

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

  • Andrey A. Poloznikov,
  • Stepan A. Nersisyan,
  • Dmitry M. Hushpulian,
  • Dmitry M. Hushpulian,
  • Eliot H. Kazakov,
  • Alexander G. Tonevitsky,
  • Sergey V. Kazakov,
  • Valery I. Vechorko,
  • Sergey V. Nikulin,
  • Julia A. Makarova,
  • Irina G. Gazaryan,
  • Irina G. Gazaryan,
  • Irina G. Gazaryan,
  • Irina G. Gazaryan

DOI
https://doi.org/10.3389/fphar.2020.621054
Journal volume & issue
Vol. 11

Abstract

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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.

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