- [HEPATIC DAMAGE AND CARCINOGENESIS]
- [GENE THERAPY AND REGULATION OF GENE EXPRESSION]
- [HEPATIC DISEASES GENE THERAPY]
- [CANCER GENE THERAPY]
Heme oxygenase-1 inducer hemin does not inhibit SARS-CoV-2 virus infection
Sheila Maestro, Karol M Córdoba, Cristina Olague, Josepmaria Argemi, Matías A Ávila, Gloria González-Aseguinolaza, Cristian Smerdou, Antonio Fontanellas
Antiviral agents with different mechanisms of action could induce synergistic effects against SARS-CoV-2 infection. Some reports suggest the therapeutic potential of the heme oxygenase-1 (HO-1) enzyme against virus infection. Given that hemin is a natural inducer of the HO-1 gene, the aim of this study was to develop an in vitro assay to analyze the antiviral potency of hemin against SARS-CoV-2 infection. A SARS-CoV-2 infectivity assay was conducted in Vero-E6 and Calu-3 epithelial cell lines.
The antiviral effect of hemin, and chloroquine as a control, against SARS-CoV-2 virus infection was quantified by RT-qPCR using specific oligonucleotides for the N gene. Chloroquine induced a marked reduction of viral genome copies in kidney epithelial Vero-E6 cells but not in lung cancer Calu-3 cells. Hemin administration to the culture medium induced a high induction in the expression of the HO-1 gene that was stronger in Vero-E6 macaque-derived cells than in the human Calu-3 cell line.
However, hemin treatment did not modify SARS-CoV-2 replication, as measured by viral genome quantification 48 h post-infection for Vero-E6 and 72 h post-infection for the Calu-3 lineages. In conclusion, although exposure to hemin induced strong HO-1 up-regulation, this effect was unable to inhibit or delay the progression of SARS-CoV-2 infection in two epithelial cell lines susceptible to infection.
CITATION Biomed Pharmacother. 2021 May;137:111384. doi: 10.1016/j.biopha.2021.111384. Epub 2021 Feb 13.