H2020Индивидуална стипендия2020–2022

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-06-01 → 2022-05-31
Финансиране от ЕС: 196 708 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Протеазата SUB1 при паразита Plasmodium се изследва чрез създаване на вещества, които да блокират излизането му от човешките клетки. Това е важно, защото паразитите стават устойчиви на текущите лекарства срещу малария и са необходими нови цели за лечение.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

Malaria is the deadliest human parasitic disease and the spreading of multi-resistant parasites seriously threatens its treatment and control. It occurs in tropical and subtropical ecosystems of more than 100 countries. Thus, about half of the world population is at risk, while the increase in human mobility (travel and migration) and climate change are causing a rise up of illness cases outside the endemic occurrence areas. The constant selection and spreading of Plasmodium parasites (falciparum and vivax, mainly) resistant to current treatments strengthens the constant need to develop antimalarials candidates active on new targets, expressed at essential stages of Plasmodium. The egress of parasite from infected host cells is such a crucial 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 antimalarials, 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 aimed at identifying highly potent and selective SUB1 inhibitors, active against parasite growth in vitro and in vivo. After two years, highly potent and selective inhibitors have been characterized, but they showed moderate parasite growth inhibition in vitro and no in vivo evaluation could be performed yet.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция