A5087137893- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- COVID-19 Clinical Research Studies
- Respiratory viral infections research
- Viral gastroenteritis research and epidemiology
- Viral Infections and Outbreaks Research
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Animal Disease Management and Epidemiology
- Long-Term Effects of COVID-19
- Immune Response and Inflammation
- Bacillus and Francisella bacterial research
- Calcium signaling and nucleotide metabolism
- Lipid Membrane Structure and Behavior
- Viral Infections and Vectors
- Retinal and Optic Conditions
- Pharmacological Receptor Mechanisms and Effects
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis B Virus Studies
- Tryptophan and brain disorders
- Cytomegalovirus and herpesvirus research
- Cytokine Signaling Pathways and Interactions
- Animal Virus Infections Studies
University of Münster
2018-2025
Institute of Virology of the Slovak Academy of Sciences
2020-2022
Institute of Molecular Biology
2016-2022
University Hospital Münster
2021
Bernhard Nocht Institute for Tropical Medicine
2009-2018
University Medical Center Freiburg
2013-2015
Institute of Medical Microbiology and Hygiene
2011-2013
University of Freiburg
2011-2013
The Coronavirus Disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Related 2 (SARS-CoV-2) is a global health emergency. As only very limited therapeutic options are clinically available, there an urgent need for rapid development of safe, effective, and globally available pharmaceuticals that inhibit SARS-CoV-2 entry ameliorate COVID-19 severity. In this study, we explored use small compounds acting on homeostasis endolysosomal host-pathogen interface, to fight...
Abstract COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, new recently emerged sarbecovirus. This virus uses the human ACE2 enzyme as receptor for cell entry, recognizing it with binding domain (RBD) of S1 subunit viral spike protein. We present use phage display to select anti-SARS-CoV-2 antibodies from naïve antibody gene libraries HAL9/10 and subsequent identification 309 unique fully against S1. 17 are RBD, showing inhibition cells expressing scFv-Fc neutralize active...
The SARS-COV-2 pandemic and the global spread of coronavirus disease 2019 (COVID-19) urgently call for efficient safe antiviral treatment strategies. A straightforward approach to speed up drug development at lower costs is repurposing. Here, we investigated therapeutic potential targeting interface SARS CoV-2 with host via repurposing clinically licensed drugs evaluated their use in combinatory treatments virus- host-directed vitro.We tested antifungal itraconazole antidepressant fluoxetine...
Significance Type I interferons (IFN-I) exhibit various biological effects during viral infections, and they have been successfully used for clinical treatment of diseases. Humans express 12 IFNα subtypes, which strongly differ in their antiviral responses against different viruses. Here we analyzed the activity all human subtypes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to identify underlying immune signatures explore therapeutic potential. Our data provide a systemic...
Abstract Coronavirus disease 2019 (COVID-19), the illness caused by a novel coronavirus now called severe acute respiratory syndrome 2 (SARS-CoV-2), has led to more than 260 million confirmed infections and 5 deaths date. While vaccination is powerful tool control pandemic spread, medication relieve COVID-19-associated symptoms alleviate progression especially in high-risk patients still lacking. In this study, we explore suitability of rapid accelerated fibrosarcoma/mitogen-activated...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis still elusive.Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied infected human lung...
Orthomyxo- and bunyaviruses steal the 5' cap portion of host RNAs to prime their own transcription in a process called "cap snatching." We report that RNA modification by 2'-O-ribose methyltransferase 1 (MTr1) is essential for initiation influenza A B virus replication, but not other cap-snatching viruses. identified with silico compound screening functional analysis derivative natural product from Streptomyces, trifluoromethyl-tubercidin (TFMT), inhibits MTr1 through interaction at its...
Human infection with highly pathogenic avian influenza viruses (HPAIV) is often associated severe tissue damage due to hyperinduction of interferons and proinflammatory cytokines. The reasons for this excessive cytokine expression are still incompletely understood, which has hampered the development efficient immunomodulatory treatment options. host protein TRIM28 associates promoter regions over 13,000 genes recognized as a genomic corepressor negative immune regulator. activity regulated...
Several studies have pointed to retinal involvement in COVID-19, yet many questions remain regarding the ability of SARS-CoV-2 infect and replicate cells its effects on retina. Here, we used human pluripotent stem cell-derived organoids study infection by SARS-CoV-2. Indeed, can organoids, as it is shown different lineages, such ganglion photoreceptors. also induces expression several inflammatory genes, interleukin 33, a gene associated with acute COVID-19 degeneration. Finally, show that...
Recent emergence of SARS-CoV-1 variants demonstrates the potential this virus for targeted evolution, despite its overall genomic stability. Here we show dynamics and mechanisms behind rapid adaptation SARS-CoV-2 to growth in Vero E6 cells. The selective advantage cells is due increased cleavage efficiency by cathepsins at mutated S1/S2 site. site also constitutes a heparan sulfate (HS) binding motif that influenced cells, but HS antagonist did not inhibit these entry E6-adapted into human...
Abstract During influenza A virus (IAV) infections, viral proteins are targeted by cellular E3 ligases for modification with ubiquitin. Here, we decipher and functionally explore the ubiquitination landscape of IAV polymerase during infection human alveolar epithelial cells applying mass spectrometry analysis immuno-purified K-ε-GG (di-glycyl)-remnant-bearing peptides. We have identified 59 modified lysines across three subunits, PB2, PB1 PA which 17 distinctively affect mRNA transcription,...
Pattern recognition receptors (PRRs) are key elements in the innate immune response. Formyl peptide receptor (FPR) 2 is a PRR that, addition to proinflammatory, pathogen‐derived compounds, also recognizes anti‐inflammatory endogenous ligand annexin A1 (AnxA1). Because contribution of this signaling axis viral infections undefined, we investigated AnxA1‐mediated FPR2 activation on influenza A virus (IAV) infection murine model. AnxA1‐treated mice displayed significantly attenuated pathology...
Influenza A virus (IAV) is a common pathogen of respiratory disease. The IAV-induced seasonal epidemics and the sporadic pandemics are associated with high morbidity mortality. Therefore, effective protection therapy for IAV infections an important challenge in countering this public health threat. Because vaccinations only protect against known circulating strains, currently available antivirals pose risk resistance formation, drugs targeting host cell factors needed viral replication offer...
The ongoing SARS-CoV-2 pandemic requires efficient and safe antiviral treatment strategies. Drug repurposing represents a fast low-cost approach to the development of new medical options. direct agent remdesivir has been reported exert activity against SARS-CoV-2. Whereas only very short half-life time bioactivation, which relies on pro-drug activating enzymes, its plasma metabolite GS-441524 can be activated through various kinases including adenosine kinase (ADK) that is moderately...
SARS-CoV-2 is the causative agent of immune response-driven disease COVID-19 for which new antiviral and anti-inflammatory treatments are urgently needed to reduce recovery time, risk death long COVID development. Here, we demonstrate that immunoregulatory kinase p38 MAPK activated during viral entry, mediated by spike protein, drives harmful virus-induced inflammatory responses. Using primary human lung explants epithelial organoids, targeting signal transduction with selective clinically...
Influenza is an acute respiratory infection causing high morbidity and mortality in annual outbreaks worldwide. Antiviral drugs are limited pose the risk of resistance development, calling for new treatment options. IFN-α subtypes immune-stimulatory cytokines with strong antiviral activities against IAV vitro vivo. However, clinical use IFN-α2, only licensed subtype this multi-gene family, could not prevent or limit infections humans. other were investigated.Therefore, study evaluated...
ABSTRACT The central domain of the 200-kDa Lassa virus L protein is a putative RNA-dependent RNA polymerase. N- and C-terminal domains may harbor enzymatic functions important for viral mRNA synthesis, including capping enzymes or cap-snatching endoribonucleases. In present study, we have employed large-scale mutagenesis approach to map functionally relevant residues in these regions. main targets were acidic (Asp Glu) basic (Lys Arg) known form catalytic binding sites A total 149 different...