A5047162578- Hepatitis C virus research
- Hepatitis B Virus Studies
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Outbreaks Research
- interferon and immune responses
- Viral Infections and Vectors
- HIV Research and Treatment
- Liver Disease Diagnosis and Treatment
- Viral gastroenteritis research and epidemiology
- Respiratory viral infections research
- Bacteriophages and microbial interactions
- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 Clinical Research Studies
- Immune Cell Function and Interaction
- Biosensors and Analytical Detection
- Disaster Response and Management
- Ocular Surface and Contact Lens
- Vector-Borne Animal Diseases
- Nicotinic Acetylcholine Receptors Study
- SARS-CoV-2 detection and testing
- Extracellular vesicles in disease
- Climate Change and Health Impacts
- Zoonotic diseases and public health
University of Nottingham
2006-2024
Loughborough University
2022-2023
St James's University Hospital
2011-2020
University of Leeds
2009-2020
King's College London
2015-2018
Guy's Hospital
2015-2017
Institute of Structural and Molecular Biology
2009-2011
ABSTRACT The hepatitis C virus (HCV) nonstructural protein NS5A is critical for viral genome replication and thought to interact directly with both the RNA-dependent RNA polymerase, NS5B, RNA. consists of three domains which have, as yet, undefined roles in assembly. In order define regions that mediate interaction RNA, specifically HCV 3′ untranslated region (UTR) positive-strand constructs different domain combinations were cloned, bacterially expressed, purified homogeneity. Each these...
ABSTRACT NS5A plays a critical, yet poorly defined, role in hepatitis C virus genome replication. The protein consists of three domains, each which is able to bind independently the 3′ untranslated region (UTR) viral positive strand genomic RNA. peptidyl-prolyl isomerase cyclophilin A (CypA) binds domain II, catalyzing cis-trans isomerization. CypA inhibitors such as cyclosporine (CsA) have been shown inhibit (HCV) We show here that stimulated II RNA binding activity, and this stimulation...
In 2005 we reported the discovery of a novel anatomical structure at limbus, which termed limbal epithelial crypt (LEC). The purpose this study was to further evaluate distribution, immunophenotypical, and ultra structural characteristics LEC as putative niche stem cells.Sequential histological sections human corneo-scleral rims were examined for presence distribution LEC. Immunophenotypical characterisation cells using panel antibodies interest undertaken. Transmission electron microscopy...
MINT‐7890784, MINT‐7890776: SH (uniprotkb:P04852) and bind (MI:0407) by electron microscopy (MI:0040)
Abstract: The hepatitis C virus (HCV) p7 ion channel plays a critical role during infectious production and represents an important new therapeutic target. Its activity is blocked by structurally distinct classes of small molecules, with sensitivity varying between isolate sequences. Although this indicative specific protein–drug interactions, lack high-resolution structural information has precluded the identification inhibitor binding sites, their modes action remain undefined....
Hepatitis C virus (HCV) chronically infects 170 million individuals, causing severe liver disease. Although antiviral chemotherapy exists, the current regimen is ineffective in 50% of cases due to high levels innate resistance. New, virus-specific therapies are forthcoming although their development has been slow and they few number, driving search for new drug targets. The HCV p7 protein forms an ion channel vitro critical secretion infectious virus. displays sensitivity several classes...
HIV-1 Vpu prevents incorporation of tetherin (BST2/ CD317) into budding virions and targets it for ESCRT-dependent endosomal degradation via a clathrin-dependent process. This requires variant acidic dileucine-sorting motif (ExxxLV) in Vpu. Structural studies demonstrate that recombinant Vpu/tetherin fusions can form ternary complex with the clathrin adaptor AP-1. However, open questions still exist about Vpu's mechanism action. Particularly, whether recruitment E3 ubiquitin ligase...
Current interferon-based therapy for hepatitis C virus (HCV) infection is inadequate, prompting a shift toward combinations of direct-acting antivirals (DAA) with the first protease-targeted drugs licensed in 2012. Many compounds are pipeline yet primarily target only three viral proteins, namely, NS3/4A protease, NS5B polymerase, and NS5A. With concerns growing over resistance, broadening repertoire DAA targets major priority. Here we describe complete structure HCV p7 protein as monomeric...
The utility of X-ray crystal structures determined under ambient-temperature conditions is becoming increasingly recognized. Such experiments can allow protein dynamics to be characterized and are particularly well suited challenging targets that may form fragile crystals difficult cryo-cool. Room-temperature data collection also enables time-resolved experiments. In contrast the high-throughput highly automated pipelines for determination at cryogenic temperatures widely available...
Hepatitis C virus (HCV) p7 protein is critical for the efficient production of infectious virions in culture. undergoes genotype-specific protein–protein interactions as well displaying channel-forming activity, making it unclear whether phenotypes deleterious mutations result from disruption one or both these functions. Here, we showed that proton channel activity alone, provided trans by either influenza M2 genotype 1b HCV p7, was necessary and sufficient to restore particle 2a (JFH-1...
ABSTRACT Type I interferon (IFN) signaling engenders an antiviral state that likely plays important role in constraining HIV-1 transmission and contributes to defining subsequent AIDS pathogenesis. II IFN (IFN-γ) also induces but is often primarily considered be immunomodulatory cytokine. We report IFN-γ stimulation can induce both distinct from of type potently inhibit primary CD4 + T cells a number human cell lines. Strikingly, we find transmitted/founder (TF) viruses resist late block...
Pandemic influenza A virus (IAV) remains a significant threat to global health. Preparedness relies primarily upon single class of neuraminidase (NA) targeted antivirals, against which resistance is steadily growing. The M2 proton channel an alternative clinically proven antiviral target, yet near-ubiquitous S31N polymorphism in evokes licensed adamantane drugs. Hence, inhibitors capable targeting N31 containing (M2-N31) are highly desirable. Rational silico design and vitro screens...
Nephropathia Epidemica (NE), endemic to several Volga regions of Russia, including the Republic Tatarstan (RT) and Mordovia (RM), is a mild form hemorrhagic fever with renal syndrome caused by infection rodent-borne orthohantaviruses. Although NE cases have been reported for decades, little known about hantavirus strains associated human in these regions. There also limited understanding pathogenesis RT RM. To address knowledge gaps, we conducted comparative analyses patients Clinical...
Early indications of the likelihood severe coronavirus disease 2019 COVID-19 can influence treatments and could improve clinical outcomes. However, knowledge on prediction markers fatality risks remains limited. Here, we analyzed quantified reactivity serum samples from acute (non-fatal fatal) convalescent patients with spike surface glycoprotein (S protein) nucleocapsid phosphoprotein (N SARS-CoV-2 peptide libraries. Cytokine activation was also analyzed. We demonstrated that IgM fatal...
Identifying immunogenic targets of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to advance diagnostic and disease control strategies. We analyzed humoral (ELISA) T-cell (ELISpot) immune responses spike (S) nucleocapsid (N) SARS-CoV-2 proteins as well human endemic coronavirus (eCoV) peptides in serum from convalescent 2019 (COVID-19) patients Tatarstan, Russia. identified multiple that were reactive with antibodies T cells COVID-19. In addition, age gender...
Since the 1960s, a single class of agent has been licensed targeting virus-encoded ion channels, or ‘viroporins’, contrasting success channel blocking drugs in other areas medicine. Although resistance arose to these prototypic adamantane inhibitors influenza A virus (IAV) M2 proton channel, growing number clinically and economically important viruses are now recognised encode essential viroporins providing potential targets for modern drug discovery. We describe first rationally designed...
In the absence of effective vaccines and treatments, annual outbreaks severe human haemorrhagic fever caused by arenaviruses, such as Lassa virus, continue to pose a significant health threat. Understanding balance cellular factors that inhibit or promote arenavirus infection may have important implications for development antiviral strategies. Here, we identified cell-intrinsic zinc transmembrane metalloprotease, ZMPSTE24, restriction factor against arenaviruses. Notably,...
Hepatitis C virus encodes an autoprotease, NS2-3, which is required for processing of the viral polyprotein between non-structural NS2 and NS3 proteins. This protease activity vital replication assembly therefore represents a target development anti-viral drugs. The mechanism this auto-processing reaction not yet clear but has been shown to map C-terminal region N-terminal serine NS3. NS2-3 precursor can be expressed in Escherichia coli as inclusion bodies, purified denatured protein...
Nephropathia epidemica (NE), caused by the hantavirus infection, is endemic in Tatarstan Russia. The majority of patients are adults, with infection rarely diagnosed children. This limited number pediatric NE cases means there an inadequate understanding disease pathogenesis this age category. Here, we have analyzed clinical and laboratory data adults children to establish whether how severity differs between two groups. Serum cytokines were samples collected from 11 129 adult during...
Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic Tatarstan. This study aimed to assess impact rosuvastatin on clinical and laboratory results NE. A total 61 NE patients 30 controls were included this study; 22 7 received daily dose (10 mg) for ten consecutive days. Serum samples collected days 1, 5, 10 after admission hospital. These analyzed determine levels lipids, cytokines, kidney toxicity...