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Engineering substrate-based inhibitors of Plasmodium SUB1, a potential target for Malaria treatment.

Descrizione del progetto

Un nuovo obiettivo per il trattamento della malaria

La malaria si conferma una delle più predominanti malattie parassitarie. L’insorgenza e la diffusione di parassiti farmacoresistenti minaccia l’efficacia dei trattamenti esistenti e richiede lo sviluppo continuo di farmaci antimalarici contro nuovi obiettivi. Il progetto SUBUN, finanziato dall’UE, indirizzerà lo sviluppo di inibitori verso la subtilisina SUB1 specifica per il plasmodio, una proteasi implicata nell’uscita del parassita dalle cellule umane infette. Ricercatori con diverse conoscenze specialistiche in chimica farmaceutica, biochimica, biologia strutturale e parassitologia si prefiggono di individuare inibitori SUB1 potenti e selettivi con valori sia profilattici che terapeutici. Questi saranno soprattutto in grado di intervenire su tutte le fasi del ciclo di vita dei parassiti, soddisfacendo i criteri dell’OMS per quanto riguarda gli agenti antimalarici.

Obiettivo

The Researcher AK Puszko will be in charge of the development of peptidase inhibitors with potential interest in the treatment of Malaria.
Malaria is the most important human parasitic disease and multi-resistant parasites seriously threaten its treatment and control. The situation strengthens the constant need to fuel the antimalarials pipeline with candidates active on new targets, expressed at essential stages of Plasmodium. The egress of merozoites from infected host cells is such a pivotal step that strictly depends upon parasite proteases, including a novel highly promising target, the Plasmodium-specific subtilisin SUB1, for which no useful inhibitor has been discovered yet. SUB1 plays a key role in the egress from hepatocytes and erythrocytes, including for male gametes (involved in parasite’s transmission via the Anopheles vector), indicating that an inhibitor would have both prophylactic and therapeutic value and obey to most severe WHO’s criteria of future anti-malarials, i.e. targeting all stages of parasite life cycle. Based on Hosts’ promising results, including the resolution of crystallographic structures of SUB1-inhibitor complexes, the SUBUN project aims at identifying highly potent and selective SUB1 inhibitors, active against parasite growth in vitro and in vivo. Such innovative pre-lead candidate(s) will be patented before results dissemination within academia, industry and to wider audience.
This project will combine expertise in molecular design, medicinal chemistry, biochemistry, structural biology and parasitology. In this multidisciplinary context, the project will benefit AK Puszko who will gain extensive knowledge in new fields well established in the Host and secondment Host laboratories. This, together with scientific and transferable trainings, opportunities to develop network, communication to non-scientific audience, will strengthen her ability to become a leader in the new topic and establish her own research group in the future.

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Coordinatore

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Contribution nette de l'UE
€ 196 707,84
Indirizzo
Rue michel ange 3
75794 Paris
Francia

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Regione
Ile-de-France Ile-de-France Paris
Tipo di attività
Research Organisations
Collegamenti
Altri finanziamenti
€ 0,00