Research and development of antiviral molecules and materials

Ente finanziatore

Banking institutions, Italian Association of Donated Human Milk Banks, Iolanda Miloni Foundation, Donations, Private Companies.

Responsabile di Progetto

David Lembo

Several projects are currently ongoing on the “Antiviral Research” area in close collaboration with chemists, biochemists, pharmaceutical technologists and physicians. These studies are applied to a wide panel of viruses for which the drug discovery represents a relevant medical need given the lack or limited availability of specific antiviral drugs. The panel of studied viruses varies according to projects and include coronaviruses, SARS-CoV-2 pseudovirions, respiratory syncytial virus, influenza viruses, rhinoviruses, adenovirus, herpesviruses, papillomaviruses, zikavirus, Usutu virus and rotaviruses.

The main objectives of “Antiviral Research” projects include:

Cell culture-based discovery of antiviral inhibitors in biosafety level 2 facilities (BSL-2). Screening of molecules library/fractions and compounds of natural origin/biological fluids are performed by cell-based high-throughput assays. Molecules with the best selectivity index are investigated to identify the inhibited step of viral replication and their potential to select resistant strains. The sequencing of the viral genome will clarify the molecular basis of resistance;
Preclinical development of lead compounds and innovative formulations ex vivo assessing their biological properties on3D models (human tissues and organoids), including the evaluation of biocompatibility, proinflammatory potentials and antiviral activity;
Identification of new antiviral materials based on nanoparticles;
Identification of new pharmacological targets against viruses by exploration the virus-host interaction;
Deepening knowledge on virus transmission via breastfeeding and antiviral properties of human milk to improve and update the International Guidelines for the Establishment and Operation of human milk banks;
Assessment of the neutralization activity of human serum samples against emerging viruses.

Sviluppo di tecniche di virologia ambientale per la rilevazione precoce e il monitoraggio di virus respiratori con potenziale pandemico

La pandemia Covid-19, sostenuta dal coronavirus SARS-CoV-2, è solo l’ultima iterazione di un fenomeno ciclico: le epidemie causate da patogeni respiratori sono eventi ricorrenti, che impattano severamente sui sistemi sanitari, sull’economia e sulla vita quotidiana. In effetti, al margine dell’attuale scenario, si disegna un orizzonte incerto rappresentato dall’impossibilità di rilevare in modo precoce l’emergere di un nuovo virus con potenziale pandemico: l’attuale approccio, infatti, delega il tracciamento dei virus alla diagnostica, limitandone la rilevazione solo dopo la comparsa dei primi contagiati.

In questo contesto, la ricerca ambientale di virus a potenziale pandemico ha un fondamentale ruolo predittivo e di monitoraggio, e tuttavia risulta ancora basata su metodologie riadattate non validate per le matrici ambientali; tali limiti compromettono qualsiasi intervento nelle fasi iniziali di una pandemia e rendono inefficace il monitoraggio della diffusione del patogeno nelle fasi più avanzate.

Il presente progetto intende colmare questo gap tecnologico, potenziando la sinergia fra l’Agenzia Regionale per la Protezione Ambientale (ARPA) del Piemonte e il Laboratorio di Virologia Molecolare e Ricerca Antivirale dell’Università di Torino, mediante lo sviluppo sperimentale di metodiche per la ricerca nell’aria e nei reflui urbani dei virus respiratori con potenziale pandemico. Tali tecniche consentiranno il rilevamento precoce dei virus, il loro isolamento e l’identificazione di varianti, nonché una più precisa e tempestiva identificazione dei focolai epidemici. Il patrimonio conoscitivo derivante da tale intervento fornirà tecnologie e strumenti per la gestione della pandemia in corso e delle future epidemie.

Risultati e pubblicazioni

Sureram S, Arduino I, Ueoka R, Rittà M, Francese R, Srivibool R, Darshana D, Piel J, Ruchirawat S, Muratori L, Lembo D, Kittakoop P, Donalisio M. The Peptide A-3302-B Isolated from a Marine Bacterium Micromonospora sp. Inhibits HSV-2 Infection by Preventing the Viral Egress from Host Cells. Int J Mol Sci. 2022 Jan 15;23(2):947.
Donalisio M, Cirrincione S, Rittà M, Lamberti C, Civra A, Francese R, Tonetto P, Sottemano S, Manfredi M, Lorenzato A, Moro GE, Giribaldi M, Cavallarin L, Giuffrida MG, Bertino E, Coscia A, Lembo D. Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro. Microorganisms. 2020 Jul 21;8(7):1087.
Francese R, Civra A, Rittà M, Donalisio M, Argenziano M, Cavalli R, Mougharbel AS, Kortz U, Lembo D. Anti-zika virus activity of polyoxometalates. Antiviral Res. 2019 Mar;163:29-33.
Civra A, Francese R, Gamba P, Testa G, Cagno V, Poli G, Lembo D. 25-Hydroxycholesterol and 27-hydroxycholesterol inhibit human rotavirus infection by sequestering viral particles into late endosomes. Redox Biol. 2018 Oct;19:318-330.
Cagno V, Andreozzi P, D'Alicarnasso M, Jacob Silva P, Mueller M, Galloux M, Le Goffic R, Jones ST, Vallino M, Hodek J, Weber J, Sen S, Janeček ER, Bekdemir A, Sanavio B, Martinelli C, Donalisio M, Rameix Welti MA, Eleouet JF, Han Y, Kaiser L, Vukovic L, Tapparel C, Král P, Krol S, Lembo D, Stellacci F. Broad- spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism. Nature Materials. 2018 Feb;17(2):195-203.

Note

The team at DSCB for this project collaborates with the following research groups:

Prof. Roberta Cavalli (Department of Drug Science and Technology, University of Turin, Turin, Italy)
Prof. Monica Ferraris (Dept. of Applied Science and Technology, Politecnico di Torino, Turin, Italy)
Prof. Enrico Bertino (Neonatal Care Unit of the University, City of Health and Science Hospital, Turin, Italy)
Italian Association of Human Milk Banks (AIBLUD – Associazione Italiana Banche del latte umano donato, Milan, Italy)
Prof. Marinella Clerico (Department of Clinical and Biological Sciences, Neurology Unit, University of Torino, Orbassano, Italy)
Prof. Alberto Bardelli (Department of Oncology, University of Turin, Candiolo, Italy)
Dr. Mario Milani (CNR-IBF, National Research Council - Biophysics Institute, Milan, Italy)
Dr. Laura Cavallarin (CNR-ISPA, National Research Council - Institute of Sciences of Food Production, Grugliasco, Italy)
Prof. Giuseppe Manfroni (Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy)
Prof. Romano Silvestri (Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy)
Prof. Ulrich Kortz (Department of Life Sciences and Chemistry, Jacobs University, Bremen, Germany),
Dr. Antoni Gayà (Balearic Islands Health Research Institute, Palma, Spain),
Prof. Prasat Kittakoop (Chulabhorn Research Institute, Bangkok, Thailand),
Prof. Guo-Chun Zhou (School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu, China)