34 projects

An integrative network-based drug repurposing approach for COVID-19

We aim at analyzing the publicly available transcriptomics data generated by exposing human lung epithelial cells to SARS-CoV particles and measuring the differences in the gene expression. We will use a molecular network analysis approach to identify a set of key genes, that represent key regulators in the SARS-CoV gene expression signature. This signature will be filtered to distinguish pathological from protective responses and used to identify drugs that could potentially reverse pathological features of the disease phenotype based on the anti-correlation of known drug-response gene exp...

Understanding Immunity in COVID-19

Previously developed model of immune response [Abulikemu et al 2020] will be modified in the collaboration with model authors and used for understanding processes involved in SARS-CoV2. We will develop a systems immunology tool that stratifies the coronavirus patient population according to (i) their likelihood of developing the cytokine tornado and (ii) the tornado subtype they are subject to. It will insert individual patient information into our Abulikemu et al model [2020] and compute the implications for whether or not a flip from moderate ('acute') inflammation to a 'cytokine tornado...

A dynamic model of the COVID-19 tuned for different countries: a systems-biological tool for the ...

A dynamic model of COVID-19 epidemics recently developed (video: https://youtu.be/lbsqJ1_WvmE, model: https://jjj.bio.vu.nl/models/westerhoff1/simulate/, ref: https://medrxiv.org/cgi/content/short/2020.03.29.20045039v1) will be tuned for different countries to analyze the effect of different measures in the anticipation of next epidemics. Models will be available for online simulations at JWS Online (https://jjj.bio.vu.nl/models/westerhoff1/simulate/), and used for the development of computer tutorials for systems biological studies.

Ultra-high sensitivity biochemical and cellular assays for diagnostics and drug discovery against...

Sensitive detection of biomolecules is the cornerstone of diagnostic and drug discovery assays in COVID-19/ SARS-CoV-2 research. Two workpackages (3 and 4) within this special LuxCOVID-19 call focus on these areas. While diagnostic assays need to be cheap, fast and reliable, drug discovery assays ideally have a strong predictive power for efficacy. Our group has developed a palette of molecular assays in the past years, in order to detect binding of small molecules or peptides to protein pockets or to protein-protein interfaces. We have a particular expertise in providing complementary in ...

Functional characterization of COVID-19 patient gut microbiome

While COVID-19 is mainly considered an airway and lung disease, up to 79% of patients present with gastrointestinal symptoms and recent studies report on the presence of SARS-CoV-2 viral RNA and particles in stools of infected patients, suggesting that the gastrointestinal (GI) tract may have a more important role in disease pathology or transmission than previously thought. The GI tract is also the site of the dense and diverse microbiome, which has the ability to regulate intestinal and systemic immunity through the conversion of dietary nutrients into bioactive metabolites. Consequently,...

Molecular Mechanisms of SARS-CoV2 - ACE2 Interactions in Covid-19

The current Covid-19 pandemic caused by the SARS-CoV2 virus is a most serious challenge for societies worldwide by endangering the health of millions of people and leading to severe socioeconomic challenges due to the implemented lockdown measures needed to manage the pandemic [1-7]. Urgently needed treatment strategies rely on the development of vaccines and antiviral drugs targeting SARS-CoV2 infections. Here, we propose to investigate the molecular mechanisms of SARS-CoV2 infections and efficiencies of potential drug interventions by molecular dynamics simulations. In particular, we will...

Development of the COVID-19 Disease Map

We develop the COVID-19 Disease Map (http://doi.org/10.17881/covid19-disease-map), a comprehensive knowledge repository of SARS-CoV-2 host-virus interaction mechanisms to support the research community and improve our understanding of the disease toward the development of efficient treatment. We share our results on github and via the FAIRDOMHub (https://fairdomhub.org/projects/190). Currently, the project gathers a large community with key international partners from the areas of pathway and molecular interaction databases, data integration and modeling. We focus on building a high-qualit...

Enabling technology for Portable, Rapid, Label-Free, PCR-Less detection of Viral RNA

Reliable detection of the presence of an infection at early stages, even before symptoms appear, is a non-trivial challenge, one that requires delivering high sensitivity in detection of viral RNA. Further, a detection at the point of care, at response times of few minutes using disposable sensors would deliver a practical solution to de-centralized mass-testing of subjects. From an industry point of view, such technology should also be practical enough to be produced and implemented in large quantities using tools that do not have to be customized. The cost of the measurement should be lo...

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