HEИндивидуална стипендия2022–2024

glyCoVdrugs · Inverting α-glucosidase inhibitors as potential drugs for SARS-CoV-2

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

Период: 2022-09-01 → 2024-08-31
Финансиране от ЕС: 203 464 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Нови инхибитори на алфа-глюкозидазните ензими се разработват, за да блокират размножаването на вируси като SARS-CoV-2. Това помага за откриването на нови антивирусни средства и подобрява готовността за справяне с бъдещи пандемии.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Inverting α-glucosidase inhibitors as potential drugs for SARS-CoV-2

The project aimed to address an urgent global health need by developing new approaches to combat viral infections such as SARS-CoV-2, the virus responsible for COVID-19. The focus was on creating inhibitors that target α-glucosidase enzymes, which are essential for the replication of various viruses, including SARS-CoV-2. Inhibiting these enzymes causes protein misfolding, leading to the controlled death of infected cells. This research was part of a broader strategy to enhance global pandemic preparedness and response. It aligned with the EU's commitment to public health, innovation, and scientific excellence, directly supporting societal needs and global challenges. The main objective was to develop a probe to screen existing libraries for new antiviral agents against SARS-CoV-2 and other viral pathogens. As powerful tool, Activity-Based Protein Profiling (ABPP) should be used as the screening method, which relies on Activity-Based Probes (ABPs, Figure 1). Since no effective covalent binding inhibitor was available, a key task of the project was the design and synthesis of suitable inhibitors. Such an inhibitor could then be converted into an ABP. This was the first time targeting covalent inhibitors for inverting glycosidases, enhancing our understanding in inhibitor design. This laid the foundation for developing and commercializing these inhibitors, helping to prevent future pandemics and improve global public health. The project’s success will also strengthen the EU’s position in pharmaceutical innovation and pandemic preparedness, opening new pathways for treatments that address global health challenges.

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

Цел на проекта

Viral infections are still a major challenge in medical therapy. The recent outbreak of SARS-CoV-2 has again shown the immense threat these pathogens pose. In contrast to the direct-acting antivirals approach (targeting viral proteases, polymerases or other viral enzymes involved in replication), which is mostly followed by the pharmaceutical industry, this proposal targeting host cell enzymes involved in the biogenesis of infectious virions. In this context inverting α-glucosidases are of special interest. They play an important role in cell functions, such as the correct folding of proteins in the endoplasmic reticulum (ER). However, up to now selective inverting α-glucosidase inhibitors are scarce, and chemical probes that report on these selectively in biological samples non-existent. The dedicated aim of this proposal is to overcome this absence of inhibitors and probes.To identify novel inhibitors, activity-based protein profiling (ABPP) will be applied. This powerful analytical method is a driving force in chemical biology and medicinal chemistry but depends heavily on the availability of mechanism-based enzyme inhibitors. Based on current knowledge on retaining α-glucosidase inhibitors, unprecedented inhibitors and probes for inverting α-glucosidases will be developed and applied to ABPP. Their synthesis follows a divergent synthesis method to efficiently produce a wide library of compounds, that will be screened on the target enzyme, human ER α-glucosidase I. As the work on retaining α-glycosidase has shown, inverting α-glucosidase inhibitors are likely to be important tools for advancing many areas of application that are outside the primary scope of the proposed research (antiviral agents). Overall, my proposal on inverting α-glycosidase inhibitors and probes will therefore make a significant contribution to the current state of the art in glycan research.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITEIT LEIDEN · LeidenКоординаторНидерландия