A5080132990- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Influenza Virus Research Studies
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- Respiratory viral infections research
- Viral Infections and Immunology Research
- Animal Diversity and Health Studies
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Peptidase Inhibition and Analysis
- Animal Disease Management and Epidemiology
- Glycosylation and Glycoproteins Research
- Vector-Borne Animal Diseases
- Virology and Viral Diseases
- Mosquito-borne diseases and control
- Advanced biosensing and bioanalysis techniques
Utrecht University
2016-2025
VIB-UGent Center for Medical Biotechnology
2024
Ghent University Hospital
2024
Ghent University
2024
Instituto de Física del Litoral
2020
Consejo Nacional de Investigaciones Científicas y Técnicas
2020
Erasmus MC
2014-2020
Ministry of Public Health
2019-2020
Seoul National University
2019-2020
Johns Hopkins University
2020
Abstract A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed detection of SARS-CoV-2 neutralizing, spike protein–specific, nucleocapsid-specific antibodies. Using serum samples from patients...
Coronavirus entry is mediated by the viral spike (S) glycoprotein. The 180-kDa oligomeric S protein of murine coronavirus mouse hepatitis virus strain A59 posttranslationally cleaved into an S1 receptor binding unit and S2 membrane fusion unit. latter thought to contain internal peptide has two 4,3 hydrophobic (heptad) repeat regions designated HR1 HR2. HR2 located close anchor, some 170 amino acids (aa) upstream it. Heptad (HR) are found in proteins many different viruses form important...
Abstract The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment this are currently lacking. Here we report monoclonal antibody that neutralizes (and SARS-CoV) cell culture. This cross-neutralizing targets communal epitope on these viruses may offer potential prevention COVID-19.
The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks deadly pneumonia. coronavirus spike (S) glycoprotein initiates infection promoting fusion viral and cellular membranes through conformational changes that remain largely uncharacterized. Here we report cryoEM structure a S postfusion state, showing large-scale secondary, tertiary, quaternary rearrangements compared with prefusion trimer rationalizing free-energy landscape...
Coronaviruses cause respiratory tract infections in humans and outbreaks of deadly pneumonia worldwide. Infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host receptors fuses viral cellular membranes. To understand molecular basis coronavirus attachment oligosaccharide receptors, we determined cryo-EM structures OC43 S glycoprotein trimer isolation complex with a 9-O-acetylated sialic acid. We show that ligand fast kinetics surface-exposed groove...
Cryo-EM and mass spectrometry analyses of the spike glycoprotein trimer from coronavirus HcoV-NL63 reveal an extensive glycan shield that covers protein surface, including epitope targeted by neutralizing antibodies against several coronaviruses. The threat a major pandemic urges development strategies to combat these pathogens. Human NL63 (HCoV-NL63) is α-coronavirus can cause severe lower-respiratory-tract infections requiring hospitalization. We report here 3.4-Å-resolution cryo-EM...
The coronavirus SARS-CoV is the primary cause of life-threatening severe acute respiratory syndrome (SARS). With aim developing therapeutic agents, we have tested peptides derived from membrane-proximal (HR2) and membrane-distal (HR1) heptad repeat region spike protein as inhibitors infection Vero cells. It appeared that HR2 peptides, but not HR1 were inhibitory. Their efficacy was, however, significantly lower than corresponding murine mouse hepatitis virus (MHV) in inhibiting MHV...
Strategies to contain the Middle East respiratory syndrome coronavirus (MERS-CoV) depend on knowledge of rate human-to-human transmission, including subclinical infections. A lack serologic tools has hindered targeted studies transmission.We studied 26 index patients with MERS-CoV infection and their 280 household contacts. The median time from onset symptoms in latest blood sampling contact was 17.5 days (range, 5 216; mean, 34.4). Probable cases secondary transmission were identified basis...
Enveloped viruses need to fuse with a host cell membrane in order deliver their genome into the cell. While some plasma membrane, many are endocytosed prior fusion. Specific cues endosomal microenvironment induce conformational changes viral fusion proteins leading and In present study we investigated entry of coronaviruses (CoVs). Using siRNA gene silencing, found that known be important for late maturation endosome-lysosome profoundly promote infection cells mouse hepatitis coronavirus...
Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. is in fact a host-range variant of the species Betacoronavirus-1 , more closely related to bovine coronavirus (BCoV)—its presumptive ancestor—and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) employ glycan-based receptors carrying 9- O -acetylated sialic acid (9- -Ac-Sia). Receptor binding mediated by spike...
Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human NL63 (HCoV-NL63). In addition hostcell receptors, lysosomal cysteine proteases are required productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of protease cathepsin L ACE2-expressing Inhibitors blocked SARS-CoV retrovirus...
We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis the whole human-derived virus and 15% camel-derived sequence yielded nucleotide polymorphism signatures suggestive cross-species transmission. Camels may act as direct source MERS-CoV infection.
Significance Middle East respiratory syndrome coronavirus (MERS-CoV) recurrently infects humans from its dromedary camel reservoir, causing severe disease with an ∼35% fatality rate. The virus binds to the dipeptidyl peptidase 4 (DPP4) entry receptor on epithelial cells via spike protein. We here report that MERS-CoV protein selectively sialic acid (Sia) and demonstrate cell-surface sialoglycoconjugates can serve as attachment factor. Our observations warrant further research into role of...
ABSTRACT Unlike other class I viral fusion proteins, spike proteins on severe acute respiratory sydrome coronavirus virions are uncleaved. As we and others have demonstrated, infection by this virus depends cathepsin proteases present in endosomal compartments of the target cell, suggesting that protein acquires its competence cleavage during cell entry rather than virion biogenesis. Here demonstrate L indeed activates membrane function protein. Moreover, was mapped to same region where,...
Abstract Dromedary camels are a putative source for human infections with Middle East respiratory syndrome coronavirus. We showed that sampled in different regions Kenya during 1992–2013 have antibodies against this virus. High densities of camel populations correlated increased seropositivity and might be factor predicting long-term virus maintenance.
Coronaviruses are enveloped viruses containing the largest reported RNA genomes. As a result of their pleomorphic nature, our structural insight into coronavirion is still rudimentary, and it based mainly on 2D electron microscopy. Here we report 3D virion structure coronaviruses obtained by cryo-electron tomography. Our study focused primarily coronavirus prototype murine hepatitis virus (MHV). MHV particles have distinctly spherical shape relatively homogenous size ( approximately 85 nm...
To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)-seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during past 30 years. We identified MERS-CoV neutralizing antibodies 81.0% from main camel-exporting countries, Sudan and Somalia, suggesting long-term virus circulation these animals.
The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often lethal illness in humans, no vaccines or specific treatments are available. Infections initiated via binding of the MERS-CoV spike (S) glycoprotein to sialosides dipeptidyl-peptidase 4 (the attachment entry receptors, respectively). To understand engagement sialylated we determined cryo-EM structures S complex with 5-N-acetyl neuraminic acid, 5-N-glycolyl sialyl-LewisX, α2,3-sialyl-N-acetyl-lactosamine...
Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) has caused an ongoing outbreak of severe acute tract infection in humans the Arabian Peninsula since 2012. Dromedary camels have been implicated as possible viral reservoirs. We used serologic assays to analyze 651 dromedary camel serum samples from United Arab Emirates; 151 were obtained 2003, well before onset current epidemic, and 500 2013. Recombinant spike protein–specific immunofluorescence virus neutralization tests...
Significance Coronaviruses exhibit a propensity for interspecies transmission, with SARS- and MERS-coronaviruses as notable examples. Cross-species transmission by coronaviruses is foremost determined the virus’ ability to bind receptors of new hosts. We here report that recently identified, yet globally distributed porcine deltacoronavirus employs host aminopeptidase N (APN) an entry receptor via S protein-mediated interaction conserved domain allows APN orthologue-mediated entry....
ABSTRACT The spike (S) protein of the recently emerged human Middle East respiratory syndrome coronavirus (MERS-CoV) mediates infection by binding to cellular receptor dipeptidyl peptidase 4 (DPP4). Here we mapped domain in S a 231-amino-acid fragment (residues 358 588) evaluating interaction truncation variants with receptor-expressing cells and soluble DPP4. Antibodies this domain—much less so those preceding N-terminal region—efficiently neutralize MERS-CoV infection.