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Article ; Online: Linked Mutations in the Ebola Virus Polymerase Are Associated with Organ Specific Phenotypes.

Dong, Xiaofeng / Tree, Julia / Banadyga, Logan / He, Shihua / Zhu, Wenjun / Tipton, Tom / Gouriet, Jade / Qiu, Xiangguo / Elmore, Michael J / Hall, Yper / Carroll, Miles / Hiscox, Julian A

Microbiology spectrum

2023 , Page(s) e0415422

Abstract: Ebola virus (EBOV) causes a severe infection called Ebola virus disease (EVD). The pathogenesis of EBOV infection is complex, and outcome has been associated with a variety of immunological and cellular factors. Disease can result from several mechanisms, ...

Abstract	Ebola virus (EBOV) causes a severe infection called Ebola virus disease (EVD). The pathogenesis of EBOV infection is complex, and outcome has been associated with a variety of immunological and cellular factors. Disease can result from several mechanisms, including direct organ and endothelial cell damage as a result of viral replication. During the2013 to 2016 Western Africa EBOV outbreak, several mutants emerged, with changes in the genes of nucleoprotein (NP), glycoprotein (GP), and the large (L) protein. Reverse genetic analysis has been used to investigate whether these mutations played any role in pathogenesis with mixed results depending on the experimental system used. Previous studies investigated the impact of three single nonsynonymous mutations (GP-A82V, NP-R111C, and L-D759G) on the fatality rate of mouse and ferret models and suggested that the L-D759G mutation decreased the virulence of EBOV. In this study, the effect of these three mutations was further evaluated by deep sequencing to determine viral population genetics and the host response in longitudinal samples of blood, liver, kidney, spleen, and lung tissues taken from the previous ferret model. The data indicated that the mutations were maintained in the different tissues, but the frequency of minor genomic mutations were different. In addition, compared to wild-type virus, the recombinant mutants had different within host effects, where the D759G (and accompanying Q986H) substitution in the L protein resulted in an upregulation of the immune response in the kidney, liver, spleen, and lungs. Together these studies provide insights into the biology of EBOV mutants both between and within hosts.
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.04154-22
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Article ; Online: Corrigendum: Inhibition of phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2.

Thursz, Mark / Sadiq, Fouzia / Tree, Julia A / Karayiannis, Peter / Beasley, David W C / Dejnirattisai, Wanwissa / Mongkolsapaya, Juthathip / Screaton, Gavin / Wand, Matthew / Elmore, Michael J / Carroll, Miles W / Matthews, Ian / Thomas, Howard

The Journal of general virology

2023 Volume 104, Issue 7

Language	English
Publishing date	2023-07-25
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001876
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Article ; Online: Inhibition of phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2.

The Journal of general virology

2023 Volume 104, Issue 7

Abstract: The 2',5'- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL ... ...

Abstract	The 2',5'- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL activity in infected cells. We aimed to investigate PDE12 as a potential pan-RNA virus antiviral drug target and develop PDE12 inhibitors that elicit antiviral activity against a range of viruses. A library of 18 000 small molecules was screened for PDE12 inhibitor activity using a fluorescent probe specific for PDE12. The lead compounds (CO-17 or CO-63) were tested in cell-based antiviral assays using encephalomyocarditis virus (EMCV), hepatitis C virus (HCV), dengue virus (DENV), West Nile virus (WNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
MeSH term(s)	Humans ; Mice ; Animals ; Rats ; Antiviral Agents/pharmacology ; SARS-CoV-2 ; COVID-19 ; RNA Viruses ; Interferon-alpha ; Encephalomyocarditis virus ; Phosphoric Diester Hydrolases
Chemical Substances	Antiviral Agents ; diethylstilbestrol monophosphate (47341-71-9) ; Interferon-alpha ; Phosphoric Diester Hydrolases (EC 3.1.4.-)
Language	English
Publishing date	2023-07-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001865
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Article ; Online: Vaccines and therapies for biodefence agents.

Tree, Julia A / Williamson, E Diane / Rowland, Caroline A / Pitt, Louise M

Journal of immunology research

2015 Volume 2015, Page(s) 537319

MeSH term(s)	Animals ; Biological Warfare/methods ; Biological Warfare Agents ; Humans ; Vaccines/immunology
Chemical Substances	Biological Warfare Agents ; Vaccines
Language	English
Publishing date	2015
Publishing country	Egypt
Document type	Editorial ; Introductory Journal Article
ZDB-ID	2817541-4
ISSN	2314-7156 ; 2314-8861
ISSN (online)	2314-7156
ISSN	2314-8861
DOI	10.1155/2015/537319
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Article ; Online: Publisher Correction: Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab')

Findlay-Wilson, Stephen / Easterbrook, Linda / Smith, Sandra / Pope, Neville / Aldridge, Matthew / Humphries, Gareth / Schuhmann, Holger / Ngabo, Didier / Rayner, Emma / Otter, Ashley / Coleman, Thomas / Hicks, Bethany / Halkerston, Rachel / Apostolakis, Kostis / Taylor, Stephen / Fotheringham, Susan / Horton, Amanda / CanoCejas, Irene / Wand, Matthew /

Tree, Julia A / Sutton, Mark / Graham, Victoria / Hewson, Roger / Dowall, Stuart

Scientific reports

2023 Volume 13, Issue 1, Page(s) 15419

Language	English
Publishing date	2023-09-18
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-42526-y
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Article ; Online: COVID-19 therapeutics: stewardship in England and considerations for antimicrobial resistance.

The Journal of antimicrobial chemotherapy

2023 Volume 78, Issue Suppl 2, Page(s) ii37–ii42

Abstract: The COVID-19 pandemic saw unprecedented resources and funds driven into research for the development, and subsequent rapid distribution, of vaccines, diagnostics and directly acting antivirals (DAAs). DAAs have undeniably prevented progression and life- ... ...

Abstract	The COVID-19 pandemic saw unprecedented resources and funds driven into research for the development, and subsequent rapid distribution, of vaccines, diagnostics and directly acting antivirals (DAAs). DAAs have undeniably prevented progression and life-threatening conditions in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are concerns of antimicrobial resistance (AMR), antiviral resistance specifically, for DAAs. To preserve activity of DAAs for COVID-19 therapy, as well as detect possible mutations conferring resistance, antimicrobial stewardship and surveillance were rapidly implemented in England. This paper expands on the ubiquitous ongoing public health activities carried out in England, including epidemiologic, virologic and genomic surveillance, to support the stewardship of DAAs and assess the deployment, safety, effectiveness and resistance potential of these novel and repurposed therapeutics.
MeSH term(s)	Humans ; COVID-19/epidemiology ; SARS-CoV-2 ; Anti-Bacterial Agents/therapeutic use ; Pandemics/prevention & control ; Antiviral Agents/therapeutic use ; Antiviral Agents/pharmacology ; Drug Resistance, Bacterial ; England/epidemiology
Chemical Substances	Anti-Bacterial Agents ; Antiviral Agents
Language	English
Publishing date	2023-11-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkad314
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 124: Show issues

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Article ; Online: Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab')

Tree, Julia A / Sutton, Mark / Graham, Victoria / Hewson, Roger / Dowall, Stuart

Scientific reports

2023 Volume 13, Issue 1, Page(s) 13912

Abstract: The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has ... ...

Abstract	The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has been used to generate candidate products. In addition to purified IgG, we have refined candidate therapies by removing non-specific IgG via affinity binding along with fragmentation to eliminate the Fc region to create F(ab')
MeSH term(s)	Cricetinae ; Animals ; Sheep ; SARS-CoV-2 ; COVID-19 ; Immunization, Passive ; Kinetics ; Immunoglobulin G
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2023-08-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-40277-4
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Article ; Online: Repeated high-dose (5 × 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits.

Tree, Julia A / Hall, Graham / Rees, Peter / Vipond, Julia / Funnell, Simon G P / Roberts, Allen D

Human vaccines & immunotherapeutics

2016 Volume 12, Issue 7, Page(s) 1795–1801

Abstract: Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was ... ...

Abstract	Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.
MeSH term(s)	Animals ; Antibodies, Viral/blood ; Drug Evaluation, Preclinical ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; Drug-Related Side Effects and Adverse Reactions/pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Injections, Subcutaneous ; Male ; Rabbits ; Smallpox Vaccine/administration & dosage ; Smallpox Vaccine/adverse effects ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/adverse effects
Chemical Substances	Antibodies, Viral ; Smallpox Vaccine ; Vaccines, Attenuated ; smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic (TU8J357395)
Language	English
Publishing date	2016-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.1080/21645515.2015.1134070
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Zs.A 6967: Show issues

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Article ; Online: Inhibition of Phosphodiesterase 12 results in Antiviral Activity against several RNA Viruses including SARS-CoV-2.

Karayiannis, Peter / Thursz, Mark / Sadiq, Fouzia / Tree, Julia / Beasley, David / Dejnirattisai, Wanwissa / Mongkolsapaya, Juthathip / Screaton, Gavin / Wand, Matthew / Elmore, Michael / Miles, Carroll / Matthews, Ian / Thomas, Howard

bioRxiv

Abstract: Phosphodiesterase 12 (PDE12) is a negative regulator of the type 1 interferon (IFN) response and here we show that PDE12 inhibitors (lead compounds 63 and 17) are associated with increased RNAseL activity, are well tolerated at the therapeutic range and ... ...

Abstract	Phosphodiesterase 12 (PDE12) is a negative regulator of the type 1 interferon (IFN) response and here we show that PDE12 inhibitors (lead compounds 63 and 17) are associated with increased RNAseL activity, are well tolerated at the therapeutic range and inhibit, both in vitro and in vivo, the replication of several RNA viruses including hepatitis C virus (HCV), dengue virus (DENV), West Nile Virus (WNV) and SARS-CoV-2.
Keywords	covid19
Language	English
Publishing date	2022-09-26
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.09.23.509178
Database	COVID19

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Article ; Online: Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence.

van Haren, Frank M P / Page, Clive / Laffey, John G / Artigas, Antonio / Camprubi-Rimblas, Marta / Nunes, Quentin / Smith, Roger / Shute, Janis / Carroll, Mary / Tree, Julia / Carroll, Miles / Singh, Dave / Wilkinson, Tom / Dixon, Barry

Critical care (London, England)

2020 Volume 24, Issue 1, Page(s) 454

Abstract: Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical ... ...

Abstract	Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes.The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low- and middle-income countries.These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.
MeSH term(s)	COVID-19 ; Coronavirus Infections/drug therapy ; Heparin/administration & dosage ; Humans ; Nebulizers and Vaporizers ; Pandemics ; Pneumonia, Viral/drug therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome
Chemical Substances	Heparin (9005-49-6)
Keywords	covid19
Language	English
Publishing date	2020-07-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-020-03148-2
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