Liberato MARZULLO | Brevetti

The primary hypothesis of our research aimed at developing a new biological antiviral therapeutic has been the possibility to shift the focus in the search of new druggable targets, with a particular interest for host cell components rather than viral determinants characterizing the traditional antiviral targeted strategies. Although this "reverse method" may be riskier for the potential increased toxicity, on the other hand it could foster the development of therapeutic tools more resilient to the obsolescence deriving from the inherent phenotypic diversity of viral targets. The recent SARS-CoV-2 pandemics pushed the research efforts in the field of vaccines and antiviral drugs development and produced a burst of literature dedicated to this topic. Among the interesting new findings (Nchioua et al., 2022; Prelli Bozzo et al., 2021), we focused our attention on the unexpected ability of SARS-CoV-2 to hijack the formerly described antiviral activity of the cell membrane protein IFITM2, exploiting indeed its presence on the cell surface to favor the fusion and the internalization of viral particles. IFITM proteins control the binding and internalization of many viruses, including SARS-CoV-2. The interaction between IFITM proteins and viruses involves conserved viral structures and the fluidity of the cell membrane, thus conditioning the general mechanism of viral infections. We isolated a highly specific anti-IFITM2 monoclonal antibody able to: • inhibit the Spike protein internalization into the host cells • reduce SARS-CoV-2 viral load • reduce Spike-induced syncytia in a human lung cell line • inhibit HSVs and RSV cytopathic effects (Basile A., et al. (2023) Spike-mediated viral membrane fusion is inhibited by a specific anti-IFITM2 monoclonal antibody. Antiviral Res. 211, 105546. https://doi.org/10.1016/j.antiviral.2023.105546)

NEED 

The innovative aspects are related to the reverse approach in the choice of a cellular mAb target, instead of a viral target. The proposed therapeutic solution could be less affected by the viral targets’ variability and more effective in the long-term treatments

VANTAGGI

The use of monoclonal antibodies can complement the adoptive choice of vaccines: - if vaccines are not available - in non-vaccinable population - in the enhancement/replacement of therapies with antiviral drugs

PRINCIPALI APPLICAZIONI

The product could be a robust and broadly applicable antiviral tool against viruses exploiting the IFITM2 docking mechanism on the plasma membrane to bind and enter into the host cell. The identification of a pharmacological tool directed against a cellular determinant that regulates the first stages of viral adhesion and invasion is also proposed as a useful aid for early or preventive treatment in all emerging viral pathologies, or those not yet sufficiently characterized, sensitive to the mechanism of inhibition mediated by the neutralization of the IFITM2 protein

TRL

TRL 4 - Tecnologia convalidata in laboratorio

PAROLE CHIAVE

Antiviral, Monoclonal antibodies, IFITM2