SarsCov2

Nox2: target of COVID-19 identified

A new study carried out by Sapienza University and Policlinico Umberto I Hospital in Rome has discovered the mechanism of action of SarsCov2 and identified the chain of reactions underlying the severe damage to the cardiorespiratory system found in patients. The results, published on Redox Biology journal, open up the prospects for new therapies

In a new study, coordinated by Francesco Violi of the Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences of Sapienza and Director of the First Medical Clinic of the Policlinico Umberto I Hospital in Rome, the researchers discovered the mechanism by which SarsCov2, responsible for the Coronavirus infection, enters the body generating a state of systemic inflammation that manifests itself with significant complications in tissues and organs.

The virus affects not only the lungs where it causes serious pneumonia often requiring mechanical ventilation, but also the heart where it is responsible for myocardial damage, and the circulatory system, where it causes serious vascular damage with increased risk of venous and arterial thrombosis. It is for this reason that the death of COVID-19 patients is often due to myocardial infarction, stroke or pulmonary embolism.

The virus enters the cells through an enzyme, called ACE2, which has an important protein degradation function, such as angiotensin II. The interaction of the virus protein with ACE2 causes loss of function of the latter, and it consequently increases the activity of angiotensin II, a powerful vasoconstrictor and mediator of inflammation of the arteries.

Previous studies had shown that angiotensin II inflammatory activity is mediated by Nox2, the most potent cellular enzyme which produces oxygen free radicals and vasoconstrictor. The research coordinated by Francesco Violi evaluated its activity through a method developed and patented in the First Medical Clinic's laboratories.

The research carried out on 182 patients, in collaboration with Claudio Mastroianni and Francesco Pugliese, both from the University Hospital Policlinico Umberto I in Rome, and published on the scientific journal Redox Biology, showed that Nox2 is activated in COVID-19 patients compared to a group of 91 healthy patients. Besides, among COVID-19 patients, it was seen that activation was more significant in those who needed mechanical ventilation or were experiencing thrombosis, suggesting a relationship between disease severity and Nox2 activation.

"These results - says Francesco Violi - explain why patients affected by COVID-19 have a severe systemic inflammation linked to damage in compensation and protective mechanisms, such as the reduction of silky levels of albumin, a phenomenon already observed in the most serious patients. In addition, they open new perspectives for combating the aggressiveness of the virus through molecules capable of inhibiting Nox2."

 

Further Info

Francesco Violi
Department of Clinical, Internal, Anesthesilogical and Cardiovascular Sciences 
francesco.violi@uniroma1.it 

 

Monday, 27 July 2020

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