SARS-CoV-2, hemoglobin and protoporphyrin IX: Interactions and perspectives

Abstract

Background: SARS-CoV-2 attacks hemoglobin through its structural protein ORF3a, dissociating the iron from the heme, as iron is necessary by cell machinery for virus replication. In this process protoporphyrin (PpIX) is released.

Methods: The decrease in the hemoglobin levels observed in patients with Covid-19 is frequently accompanied by an increase in PpIX levels. This evidence was confirmed by the quantification of PpIX by high-performance liquid chromatography (HPLC). PpIX emission is observed in its two characteristic bands at approximately 635 nm and 705 nm.

Results: This paper searches to understand the role of heme and PpIX inside the cells. Perspectives on the use of PpIX fluorescence as a sensor to monitor the presence of SARS-CoV-2 in the tissue, blood, urine, or feces to map the evolution and severity of the disease or to monitor the response of the Covid-19 treatment modalities were described.

Conclusion: Fluorescence spectroscopy could be adopted as an excellent diagnostic technique for Covid-19, of low cost and high sensitivity. This method can potentially be used as a marker to monitor the response to the treatments. Photodynamic and sonodynamic therapies using the endogenous PpIX increased in the acute phase of the disease, could be employed for Covid-19 treatment.

Keywords: Covid-19; Fluorescence; Hemoglobin; Protoporphyrin IX.

Fig. 1

Direct infection of specific erythroid progenitors, ERP-S2 and ERP-S3 by SARS-CoV-2 [43]. Hemoglobin structure with the alpha chains (α1, α2), the beta chains (β1, β2), and the four heme groups. On the right the structure of the iron protoporphyrin IX subunit of heme B.

Fig. 2

a) Calibration curve of synthetic protoporphyrin IX prepared in acetone (Sigma). b) PpIX was extracted from blood samples from thirty people without Covid-19 and blood disorders. PpIX fluorescence was obtained under excitation at 410 nm and the presented spectrum is an average of the thirty spectra.