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Frontiers Pharmacology magazine published an article «HIF Prolyl Hydroxylase Inhibitors for COVID-19 Treatment: Pros and Cons»

A collaborative study by a group of scientists from the International Laboratory for Microphysiological Systems has been published that analyzes the potential benefits and challenges of using HIF prolyl hydroxylase inhibitors as a treatment for COVID-19

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.

In 2019, a spike in the cases of lethal pneumonia caused by the global spread of the SARS-CoV-2 virus led to an urgent need to develop effective therapies, especially vaccines (Chan et al., 2020;Zhou et al., 2020). The virus belongs to the Coronaviridae family, which consists of 40 enveloped viruses containing single-stranded (+)RNA (Holmes, 2001;Lai and Holmes, 2001). Most of these viruses frequently circulate in human populations, causing non-life threatening intestinal and respiratory infections (Corman et al., 2019). However, some members of the family such as the severe acute respiratory syndrome (SARS-CoV) and the Middle East respiratory syndrome (MERS-CoV) coronaviruses cause severe illnesses (Fehr et al., 2017). The tropism of the SARS-CoV-2 virus, the structure of its receptor binding domain, the virus’s mechanism of entry into the target cell and its life cycle are well documented in (McKee et al., 2020;Sternberg et al., 2020). SARS-CoV infection also disrupts gastrointestinal tract function, as evidenced by the presence of the virus in biopsy and in stool samples even in discharged patients (Leung et al., 2003). SARS-CoV infection leads to the damage of the respiratory system and to thrombosis, and is accompanied by hypoxia which contributes to the severity of disease. Very recently a number of warnings have been reported with respect to CNS damage and long-term side effects in patients who have recovered from COVID-19 (the infectious disease caused by SARS-CoV-2 virus).

In this paper we focus on the possibility of using anti-hypoxic drugs under development to prevent, treat, or ease the long-term side effects of COVID-19.