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.
The obtained results will contribute to clarify the mechanisms at the basis of lung pathogenesis caused by respiratory viruses, such as SARS-CoV2 and influenza virus infection as well as the regulation of ACE2 expression by redox-related pathways.
The use of antioxidant molecules in a cell based-therapy strategy represents a promising approach to treat different types of viral infections. Indeed, the possibility to modulate redox-related pathways used in common by different viruses for their replication but also regulating inflammatory response, could overcome the emergence of drug resistant strains that is the limit of therapy based on targeting viral proteins.
This therapeutic approach may contribute to counteract the emergence of COVID-19 for which there is an urgent need to search a valid therapeutic option.