22 projects

Impact of hypoxia on COVID-19 infection in lung epithelial cells

The international spread of coronavirus disease 2019 (COVID-19) has recently caused over 120.000 deaths in Europe and 200.000 worldwide. The clinical picture goes from the absence of symptoms to critical conditions requiring admission to resuscitation units. The molecular pathways involved in COVID-19 infection and pathogenesis are still being explored. 'Silent hypoxia' is considered by some physicians as an early indicator of COVID-19 viral infection in patients. A key step in COVID-19 infection is the viral entry into pulmonary alveoli epithelial cells, leading to the disruption of surf...

Comparative antiviral efficacy of different autophagy inhibitors against COVID-19 infection

As of April 28, 2020, worldwide, over 3 million people have been diagnosed and over 211,000 deaths with ongoing deadly coronavirus disease-19 (COVID-19) also known as SARS coronavirus 2 (SARS-CoV-2/2019-nCoV). Currently, there is no approved treatment against COVID-19. Vaccines are under development, but they will take at least one year before reaching to the population. A fast track approach would be to reuse already approved drugs that have been broadly tested through multiple clinical trials. Virophagy is a catabolic autophagic pathway used by mammalian cells to destroy viruses. Viruses ...

Leveraging Systems Biology to Target Hyperinflammation in COVID-19

The emergence of COVID-19 pandemic implies new challenges for the Health Systems worldwide. A small percentage of the patients require hospitalisation and specialised attention in Intensive Care Units (ICUs). Furthermore, accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. Therefore, the main goal of the proposal is to elucidate the potential role of cytokine storm in COVID-19 disease severity, and to propose novel strategies for counteracting this hyperinflammatory response. In this context, we propose to develop a single...

Cytokines as biomarkers and therapeutic targets in COVID-19 infection

Cytokines play an important role in the pathogenesis of COVID-19 infection. A subgroup of patients develops a cytokine storm syndrome, correlating with a bad clinical outcome. For example, the concentration of the inflammatory cytokine Interleukin-6 (IL-6) has been recognized as a risk factor for mortality and for respiratory failure in Chinese and German patient cohorts, respectively. Tocilizumab, an antibody directed against the IL-6 receptor alpha chain, is used in clinical trials as well as an FDA-approved inhibitor of Jaks, tyrosine kinases which mediate the signal transduction of mult...

Virus-Surface Interactions in Dynamic Environments (V-SIDE)

Since the recent outbreak of the COVID-19 pandemic, a growing body of scientific literature has reported on the pre-infection viability and stability of the SARS-CoV-2 virus, qualitatively indicating the role of physical surfaces in transmission of the virus. The nature of the surfaces (e.g., paper v/s plastic v/s metals) and their properties (smooth v/s rough), are believed to play a critical role in determining the stability and viability during the pre-infection phase. Virus-surface interactions are inherently biophysical in nature wherein the dynamics of the environmental parameters (va...

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...

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,...

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