AUTHOR=Poloznikov Andrey A. , Nersisyan Stepan A. , Hushpulian Dmitry M. , Kazakov Eliot H. , Tonevitsky Alexander G. , Kazakov Sergey V. , Vechorko Valery I. , Nikulin Sergey V. , Makarova Julia A. , Gazaryan Irina G. TITLE=HIF Prolyl Hydroxylase Inhibitors for COVID-19 Treatment: Pros and Cons JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.621054 DOI=10.3389/fphar.2020.621054 ISSN=1663-9812 ABSTRACT=

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.