• Hemopexin, the plasma scavenger of heme, accumulates at the site of tissue injury to
limit heme toxicity. Moreover, it has been shown that hemopexin can promote heme
efflux through FLVCR1a. Do heme scavengers modulate cell metabolism in a way that
sustain Sars-CoV2 infection?
• Interestingly, FLVCR1 is a hypoxia responsive gene. Thus, hypoxia is expected to
enhance the heme synthesis-export system to down-modulate oxidative metabolism.
On the other hand, low oxygen tension promotes glycolysis. Targeting HIFs and/or the
heme synthesis-export system may have therapeutic potential for the development
of new treatments for COVID19.
References
1. Wagener FADT, Pickkers P, Peterson SJ, Immenschuh S, Abraham NG. Targeting the Heme-
Heme Oxygenase System to Prevent Severe Complications Following COVID-19 Infections. Antioxidants
(Basel). 2020;9(6).
2. Rossi M, Piagnerelli M, Van Meerhaeghe A, Zouaoui Boudjeltia K. Heme oxygenase-1 (HO-1)
cytoprotective pathway: A potential treatment strategy against coronavirus disease 2019 (COVID-19)-
induced cytokine storm syndrome. Med Hypotheses. 2020;144:110242.
3. Mayer KA, Stöckl J, Zlabinger GJ, Gualdoni GA. Hijacking the Supplies: Metabolism as a Novel
Facet of Virus-Host Interaction. Front Immunol. 2019;10:1533.
4. Codo AC, Davanzo GG, Monteiro LB, et al. Elevated Glucose Levels Favor SARS-CoV-2 Infection
and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis. Cell Metab. 2020;32(3):437-
446.e435.
5. Bojkova D, Klann K, Koch B, et al. Proteomics of SARS-CoV-2-infected host cells reveals
therapy targets. Nature. 2020;583(7816):469-472.
6. Fiorito V, Allocco AL, Petrillo S, et al. The heme synthesis-export system: a regulator of the
tricarboxylic acid cycle flux and oxidative phosphorylation. Cell Reports, under revision; 2021.