rSAMs-NANO · Nanoparticles with switchable shells for virus sensing and inhibition
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-09-03 → 2020-09-02
- EU contribution
- €185,857
- Participants
- 1
- Scheme
- MSCA-IF-EF-CAR
Lines connect the coordinator with its partners.
Results in brief
Nanoparticles with switchable shells for virus sensing and inhibition
The development of antiviral drugs and virus sensors remains a challenge in the field of medical therapies and diagnosis. The current approach for the design of new antiviral drug candidates relies on the synthesis of monovalent drugs that inhibit virus replication at the late stage of infection. The existing antiviral treatment however suffers from low effectiveness due to the emerging drug resistance mutation. In this context, the development of synthetic drugs with multivalent ligand representation is considered an advantageous alternative for the treatment of severe viral infections such as Influenza. Influenza is an acute respiratory disease and can spread rapidly and widely in the winter season. About 20% of children and 5% of adults worldwide develop symptomatic influenza each year. It causes a broad range of illnesses, from symptomless infection to primary viral and secondary bacterial pneumonia. Rapid diagnosis of influenza viruses during an outbreak is critical for disease control. There are currently three types of diagnostic tests for influenza viruses: virus isolation, antigen capture immunoassays, and molecular diagnostic tests. Although effective and sensitive, these methods require trained personnel and a long testing time. Hence, the development of probes and sensors capable of rapid typing and subtyping of the influenza virus is highly desirable. The current design of the new efficient drugs and diagnostics of Influenza includes the synthesis of complex multivalent compounds as dendrimers, fullerenes, polymers, etc. and requires time-consuming multistep organic synthesis. In this project, we applied the rSAM technique for the engineering of multivalent virus inhibitors and the development of the new effective sensors that can provide flexible recognition of the influenza viruses. The rSAMs are pH-switchable versions of thiol-SAMs monolayers that mimic the complex multivalent carbohydrate arrays present on the cellular surfaces. The rSAMs can be constructed using easily accessible small ligands that allow avoiding the above-mentioned synthetic limitations. The main objectives of the rSAM-NANO project were 1) to investigate the use of rSAMs as dynamic nanoparticle shells for multivalent inhibition of pathogen infection and colonization, and 2) to assess such systems as new antibody-free ultrasensitive and robust sensors for rapid in situ virus diagnostics and viral load of the patient.
Data: CORDIS, © European Union
Project objective
This proposal concerns Reversible Self-assembled Monolayers (rSAMs) as dynamic nanoparticle shells for multivalent interactions at biointerfaces. Current drug design and diagnostics are exploring the multivalency concept, i.e. binding of biological targets via multiple weak interactions. In contrast to classical drug design relying on high-affinity inhibitors, thisrelies on dendritic architectures featuring a high density of ligands, e.g. saccharides, capable of simultaneously interacting with biointerfacial receptors. This strategy can be used to inhibit the virus entry by blocking the receptor at the early stages of infection and the concept is being explored as antiviral drugs and in virus sensing. However, in current systems ligands are covalently fixed on the particle surface. This prevents control over the ligand distribution and composition which compromises selectivity and affinity of the interactions. rSAMs are pH-switchable versions of thiol-SAMs. They are tunable with respect to the nature of the head group and layer order and stability while featuring pH responsiveness and the dynamic nature of non-covalently build assemblies e.g. lipid bilayers. Ligand decorated rSAMs therefore feature strongly enhanced affinities for multivalent targets. The main aims of this proposal are:1) to investigate the use of rSAMs as dynamic nanoparticle shells for multivalent inhibition of viruses and 2) to assess suchsystems as nanoplasmonic sensors for antibody-free ultrasensitive, robust and rapid in situ virus detection.Under 1) we will select model pathogens, e.g. Ebola and prepare a series of saccharide terminated amidines for the first generation dynamic shell nanoparticles.Their efficiency will be assessed in infection assays using artificial virus particlesUnder 2) we will develop influenza virus sensors with subtyping capability within human and animal virus strains. The sensors will be validated with respect to benchmark assays.
Original text from CORDIS.
Participants
- MALMO UNIVERSITET · MALMOECoordinatorSweden
Links
Data: CORDIS, © European Union