ROMA (ITALPRESS) – A team of researchers from the Department of Biomedicine and Prevention of the University of Rome Tor Vergata, in collaboration with the European Research Infrastructure on Highly Pathogenic Agents (ERINHA) and other Italian and Hungarian institutions, today published in the Journal of Cellular and Molecular Medicine a preclinical study that assesses the therapeutic effectiveness of Indolo3-Carbinol (Indolo3-.
The I3C is a natural compound present in high concentrations in the vegetables of the Brassicaceae family, such as broccoli, cabbage and cauliflowers. Previous in vitro studies had already demonstrated its ability to inhibit the release of the SARS-CoV-2 virus from infected cells, acting as an inhibitor of HECT E3 ubiquitin ligasi, essential enzymes for the vital cycle of the virus. This study represents the first step towards preclinical validation in vivo of this molecule.
An animal model that replicates human pathology The researchers used the model of golden Syrian hamster (Mesocricetus auratus), widely recognized for its ability to faithfully replicate the pathological characteristics of SARS-CoV-2 infection in man, including acute respiratory distress syndrome (ARDS). Animals were infected with the Delta variant of the virus and treated intraperitoneally with two doses of I3C (2 mg and 4 mg).
The results showed that the dose of 2 mg of I3C was able to: Significantly reduce the viral load in the lungs of treated animals; Improve clinical scores of disease, with a delay in the appearance of symptoms and a decrease in weight loss; Decrease the alveolar pulmonary edema, one of the main pathological factors at the base of the ARDS; Break down the levels of TNF-a (Tumor Necrosis Factor-alpha), a key pro-inflammatory cytokin responsible for the “cytokinenic rhythm” that characterizes the severe forms of COVID-19, both at the pulmonary and systemic level (in the serum).
On the contrary, the highest dose (4 mg) showed signs of toxicity, indicating the presence of a clear therapeutic window for the compound. A double mechanism of action: antiviral and anti-inflammatory “Our data shows that I3C has a dual mechanism of action that makes it particularly interesting for the treatment of COVID-19”, said Giuseppe Novelli, Ordinary of Medical Genetics at the University of Rome Tor Vergata and coordinator of the study.
“On the one hand, it acts directly on the virus, inhibiting the release from infected cells; on the other, it modulates the host’s inflammatory response, reducing TNF-a levels and limiting tissue damage. This combination is rare and particularly valuable in pathologies such as ADS, where inflammation is the main factor of mortality.”.
“The fact that I3C acts on cell mechanisms preserved and not on a specific viral target makes it an ideal candidate not only for COVID-19, but also for future pandemics from other respiratory viruses that share the same inflammatory pathogenesis,” added Pier Paolo Pandolfi, co-author of the study and professor at the University of Turin.
The study, supported by the Ministry of University and Research (PNRR M4-C2-1.1 PRIN2022 “HECORES” and PNRR M4-C2-1.4 CN00000041), by the European project “UNDINE” (HORIZON-HLTH-2021-DISEASE-04-07), and by the Rome Foundation, lays the foundations for clinical trial in man. The I3C, being a natural compound already known and with a favorable safety profile, could represent an additional therapy, easily accessible and at low cost, for the treatment of viral respiratory infections.
“The next steps will be the clinical trial design to assess the effectiveness and safety of I3C in patients with COVID-19 and, potentially, in other viral respiratory syndromes,” concluded Novelli. “Our study shows that nature still offers valuable resources for pharmacological research, and that investing in preclinical research is essential to be ready to face future health challenges.”.
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