A5071095963- SARS-CoV-2 and COVID-19 Research
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Autophagy in Disease and Therapy
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Phagocytosis and Immune Regulation
- Viral Infections and Outbreaks Research
- Erythrocyte Function and Pathophysiology
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- Computational Drug Discovery Methods
- Respiratory viral infections research
- Cannabis and Cannabinoid Research
- Mosquito-borne diseases and control
- RNA Research and Splicing
- Biosensors and Analytical Detection
- RNA modifications and cancer
- Transgenic Plants and Applications
- SARS-CoV-2 detection and testing
- RNA Interference and Gene Delivery
- Infection Control and Ventilation
The Francis Crick Institute
2020-2024
University of Cambridge
2018-2021
Biology of Infection
2020-2021
University College London
2020
University College London Hospitals NHS Foundation Trust
2020
National Hospital for Neurology and Neurosurgery
2020
Utrecht University
2013-2019
Radboud University Nijmegen
2014-2015
Radboud University Medical Center
2014-2015
Radboud Institute for Molecular Life Sciences
2015
Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected humoral immunity. spike glycoprotein (S)-reactive were detectable using a flow cytometry-based method SARS-CoV-2-uninfected individuals and particularly prevalent children adolescents. They predominantly the immunoglobulin G (IgG) class targeted S2 subunit. By contrast, infection induced higher titers S-reactive IgG...
Article9 January 2018Open Access Transparent process The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation LC3 at single membranes Katherine Fletcher Signalling Programme, Babraham Institute, Cambridge, UK Search more papers by this author Rachel Ulferts Division Virology, Department Pathology, University Elise Jacquin Talitha Veith Noor Gammoh Edinburgh Cancer Research Centre, Edinburgh, Julia M Arasteh Norwich Medical School, UEA, Norwich, Ulrike Mayer School...
Autophagy is a fundamental catabolic process that uses unique post-translational modification, the conjugation of ATG8 protein to phosphatidylethanolamine (PE). lipidation also occurs during non-canonical autophagy, parallel pathway involving single membranes (CASM) at endolysosomal compartments, with key functions in immunity, vision, and neurobiology. It widely assumed CASM involves same PE, but this has not been formally tested. Here, we discover all ATG8s can undergo alternative...
SARS-CoV-2 spike N-terminal domain harbors a potent epitope that can be modulated by binding of natural linear tetrapyrroles.
In mammals, early resistance to viruses relies on interferons, which protect differentiated cells but not stem from viral replication. Many other organisms rely instead RNA interference (RNAi) mediated by a specialized Dicer protein that cleaves double-stranded RNA. Whether RNAi also contributes mammalian antiviral immunity remains controversial. We identified an isoform of Dicer, named (aviD), protects tissue viruses-including Zika virus and severe acute respiratory syndrome coronavirus 2...
The approximately 30-kb coronavirus (+)RNA genome is replicated and transcribed by a membrane-bound replicase complex made up of 16 viral nonstructural proteins (nsp) with multiple enzymatic activities. includes an RNA endonuclease, NendoU, that conserved among nidoviruses but no other virus, making it genetic marker this virus order. NendoU (nsp15) Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond. Neither biochemical nor sequence...
The genus Enterovirus of the family Picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71) for which no antiviral drugs are available. viral RNA-dependent RNA polymerase is an attractive target therapy. Nucleoside-based inhibitors have broad-spectrum activity but often exhibit off-target effects. Most non-nucleoside (NNIs) surface cavities, structurally more flexible than nucleotide-binding pocket, hence a narrow spectrum...
Abstract Several related human coronaviruses (HCoVs) are endemic in the population, causing mild respiratory infections 1 . Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), etiologic agent of disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic proportions 2,3 Zoonotic introduction novel thought to occur absence pre-existing immunity target population. Using diverse assays for detection antibodies reactive with SARS-CoV-2 spike (S)...
We document here that intensive care COVID-19 patients suffer a profound decline in hemoglobin levels but show an increase of circulating nucleated red cells, suggesting SARS-CoV-2 infection either directly or indirectly induces stress erythropoiesis. ACE2 expression peaks during erythropoiesis and renders erythroid progenitors vulnerable to by SARS-CoV-2. Early progenitors, defined as CD34
The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome 2 (SARS-CoV-2), a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there need for therapeutics. Repurposing existing drugs represents promising potentially rapid opportunity to find novel antivirals SARS-CoV-2. encodes at least nine enzymatic activities that are potential drug targets. Here, we have expressed,...
SARS-CoV-2 is responsible for COVID-19, a human disease that has caused over 2 million deaths, stretched health systems to near-breaking point and endangered economies of countries families around the world. Antiviral treatments combat COVID-19 are currently lacking. Remdesivir, only antiviral drug approved treatment can affect severity, but better needed. encodes 16 non-structural proteins (nsp) possess different enzymatic activities with important roles in viral genome replication,...
The COVID-19 pandemic has emerged as the biggest life-threatening disease of this century. Whilst vaccination should provide a long-term solution, is pitted against constant threat mutations in virus rendering current vaccines less effective. Consequently, small molecule antiviral agents would be extremely useful to complement program. causative agent novel coronavirus, SARS-CoV-2, which encodes at least nine enzymatic activities that all have drug targeting potential. papain-like protease...
The coronavirus 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), spread around world with unprecedented health and socio-economic effects for global population. While different vaccines are now being made available, very few antiviral drugs have been approved. main viral protease (nsp5) of SARS-CoV-2 provides an excellent target antivirals, due to its essential conserved function in replication cycle. We expressed, purified developed assays nsp5...
ABSTRACT Nidoviruses (arteriviruses, coronaviruses, and roniviruses) are a phylogenetically compact but diverse group of positive-strand RNA viruses that includes important human animal pathogens. Nidovirus synthesis is mediated by cytoplasmic membrane-associated replication/transcription complex up to 16 viral nonstructural proteins (nsps), which carry common enzymatic activities, like the polymerase, also unusual poorly understood RNA-processing functions. Of these, conserved...
Although the genus Enterovirus contains many important human pathogens, there is no licensed drug for either treatment or prophylaxis of enterovirus infections. We report that fluoxetine (Prozac)--a selective serotonin reuptake inhibitor--inhibits replication B (HEV-B) and HEV-D but does not affect HEV-A HEV-C rhinovirus A B. show interferes with viral RNA replication, we identified protein 2C as target this compound.
Enteroviruses (EVs) represent many important pathogens of humans. Unfortunately, no antiviral compounds currently exist to treat infections with these viruses. We screened the Prestwick Chemical Library, a library approved drugs, for inhibitors coxsackievirus B3, identified pirlindole as potent novel inhibitor, and confirmed inhibitory action dibucaine, zuclopenthixol, fluoxetine, formoterol. Upon testing viruses several EV species, we found that dibucaine inhibited EV-B EV-D also EV-A, but...
Enteroviruses (family Picornaviridae) comprise a large group of human pathogens against which no licensed antiviral therapy exists. Drug-repurposing screens uncovered the FDA-approved drug fluoxetine as replication inhibitor enterovirus B and D species. Fluoxetine likely targets nonstructural viral protein 2C, but detailed mode-of-action studies are missing because structural information on 2C fluoxetine-sensitive enteroviruses is lacking. We here show that broad-spectrum anti-enteroviral...
RNA structural elements occur in numerous single-stranded positive-sense viruses. The stem-loop 2 motif (s2m) is one such element with an unusually high degree of sequence conservation, being found the 3' untranslated region (UTR) genomes many astroviruses, some picornaviruses and noroviruses, a variety coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV) SARS-CoV-2. evolutionary conservation its occurrence all viral subgenomic transcripts imply key role for s2m...
Although commonly associated with autophagosomes, LC3 can also be recruited to membranes by covalent lipidation in a variety of non-canonical contexts. These include responses ionophores such as the M2 proton channel influenza A virus. We report subtractive CRISPR screen that identifies factors required for lipidation. As well enzyme complexes directly responsible all contexts, we show RALGAP complex is important M2-induced, but not ionophore drug-induced, In contrast, ATG4D recycling...
The COVID-19 pandemic has presented itself as one of the most critical public health challenges century, with SARS-CoV-2 being third member Coronaviridae family to cause a fatal disease in humans. There is currently only antiviral compound, remdesivir, that can be used for treatment COVID-19. To identify additional potential therapeutics, we investigated enzymatic proteins encoded genome. In this study, focussed on viral RNA cap methyltransferases, which play key roles enabling protein...
Abstract Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based England, looked at spike-specific immune 341 staff and residents long-term care facilities received an mRNA vaccine following dual series with BNT162b2 or ChAdOx1. strongly increased antibody...
Members of the Enterovirus (poliovirus [PV], coxsackieviruses, and human rhinoviruses) Kobuvirus (Aichi virus) genera in Picornaviridae family rely on PI4KIIIβ (phosphatidylinositol-4-kinase IIIβ) for efficient replication. The small membrane-anchored enteroviral protein 3A recruits to replication organelles, yet underlying mechanism has remained elusive. Recently, it was shown that kobuviruses recruit through interaction with ACBD3 (acyl coenzyme A [acyl-CoA]-binding domain 3), a novel...