The role of redox state in modulating ACE2 expression: a cell targeting based-approach for the treatment of SARS-CoV2 pathogenesis and inflammation

Proponente Lucia Nencioni - Professore Ordinario
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca
Componente Categoria
Marta De Angelis Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca

The huge impact of SARS-CoV2 infection on the health care systems, economy and common life styles led to the emergence of discover new therapeutic approaches. A common feature for different types of viral infections is the induction of an oxidative stress condition into host cell. The cell-based therapy approach, by using specific antioxidant molecules, represents a promising strategy against respiratory viruses. ACE2, the receptor of SARS-CoV2 infection, is strictly related to redox-regulated pathways and inflammation and its down-regulation during respiratory viral infection is related to the induction of the lung injury.
Based on these evidences in the present proposal we wonder to clarify the mechanisms by which redox-sensitive pathways activated by SARS-CoV2 and influenza virus infection are related to ACE2 modulation. Furthermore, we will evaluate the potential antiviral effect of specific antioxidant molecules (GSH-C4, NAC and I-152) and whether these compounds may interfere with ACE2 expression.
In detail, the specific objectives will be the following:
a) to evaluate the modulation of ACE2 expression and the redox state parameters after SARS-CoV2 infection;
b) to test the antiviral activity of antioxidant molecules against SARS-CoV2 and influenza virus infections, focusing on their effects on ACE2 expression and redox-related pathways;
c) to analyze the effect of the selected antiviral molecules on antioxidant and inflammatory pathways, such as Nrf2-mediated one, studying the expression of related antioxidant/inflammatory genes and of their protein products.
Our results will provide new knowledge on the mechanisms underlying SARS-CoV2 and influenza virus pathogenesis and will identify new promising molecules for the treatment of flu and COVID-19.

LS6_6, LS6_7, LS3_5

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