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Article ; Online: Advances in diagnostics, vaccines and therapeutics for Nipah virus.

Thakur, Nazia / Bailey, Dalan

2019 Volume 21, Issue 7, Page(s) 278–286

Abstract: Nipah virus is an emerging zoonotic paramyxovirus that causes severe and often fatal respiratory and neurological disease in humans. The virus was first discovered after an outbreak of encephalitis in pig farmers in Malaysia and Singapore with subsequent ...

Abstract	Nipah virus is an emerging zoonotic paramyxovirus that causes severe and often fatal respiratory and neurological disease in humans. The virus was first discovered after an outbreak of encephalitis in pig farmers in Malaysia and Singapore with subsequent outbreaks in Bangladesh or India occurring almost annually. Due to the highly pathogenic nature of NiV, its pandemic potential, and the lack of licensed vaccines or therapeutics, there is a requirement for research and development into highly sensitive and specific diagnostic tools as well as antivirals and vaccines to help prevent and control future outbreak situations.
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; Clinical Laboratory Techniques ; Disease Outbreaks/prevention & control ; Henipavirus Infections/diagnosis ; Henipavirus Infections/epidemiology ; Henipavirus Infections/prevention & control ; Henipavirus Infections/therapy ; Humans ; Models, Biological ; Nipah Virus/genetics ; Nipah Virus/immunology ; Nipah Virus/isolation & purification ; Nipah Virus/pathogenicity ; Viral Vaccines/immunology ; Zoonoses/epidemiology ; Zoonoses/transmission
Chemical Substances	Antiviral Agents ; Viral Vaccines
Language	English
Publishing date	2019-02-26
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1465093-9
ISSN	1769-714X ; 1286-4579
ISSN (online)	1769-714X
ISSN	1286-4579
DOI	10.1016/j.micinf.2019.02.002
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Article ; Online: Production of Recombinant Replication-defective Lentiviruses Bearing the SARS-CoV or SARS-CoV-2 Attachment Spike Glycoprotein and Their Application in Receptor Tropism and Neutralisation Assays.

Thakur, Nazia / Gallo, Giulia / Elreafey, Ahmed M E / Bailey, Dalan

Bio-protocol

2021 Volume 11, Issue 21, Page(s) e4249

Abstract: For enveloped viruses, such as SARS-CoV-2, transmission relies on the binding of viral glycoproteins to cellular receptors. Conventionally, this process is recapitulated in the lab by infection of cells with isolated live virus. However, such studies can ...

Abstract	For enveloped viruses, such as SARS-CoV-2, transmission relies on the binding of viral glycoproteins to cellular receptors. Conventionally, this process is recapitulated in the lab by infection of cells with isolated live virus. However, such studies can be restricted due to the availability of high quantities of replication-competent virus, biosafety precautions and associated trained staff. Here, we present a protocol based on pseudotyping to produce recombinant replication-defective lentiviruses bearing the SARS-CoV or SARS-CoV-2 attachment Spike glycoprotein, allowing the investigation of viral entry in a lower-containment facility. Pseudoparticles are produced by cells transiently transfected with plasmids encoding retroviral RNA packaging signals and
Language	English
Publishing date	2021-11-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325 ; 2331-8325
ISSN (online)	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.4249
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Article ; Online: ChAdOx1 nCoV-19 vaccination generates spike-specific CD8

Foster, William S / Newman, Joseph / Thakur, Nazia / Spencer, Alexandra J / Davies, Sophie / Woods, Danielle / Godfrey, Leila / Ross, Sarah H / Sharpe, Hayley J / Richard, Arianne C / Bailey, Dalan / Lambe, Teresa / Linterman, Michelle A

Immunology and cell biology

2023 Volume 101, Issue 6, Page(s) 479–488

Abstract: Effective vaccines have reduced the morbidity and mortality caused by severe acute respiratory syndrome coronavirus-2 infection; however, the elderly remain the most at risk. Understanding how vaccines generate protective immunity and how these ... ...

Abstract	Effective vaccines have reduced the morbidity and mortality caused by severe acute respiratory syndrome coronavirus-2 infection; however, the elderly remain the most at risk. Understanding how vaccines generate protective immunity and how these mechanisms change with age is key for informing future vaccine design. Cytotoxic CD8
MeSH term(s)	Animals ; Humans ; Mice ; CD8-Positive T-Lymphocytes ; ChAdOx1 nCoV-19 ; COVID-19/prevention & control ; Vaccination ; T-Lymphocytes, Cytotoxic ; Antibodies, Viral
Chemical Substances	ChAdOx1 nCoV-19 (B5S3K2V0G8) ; Antibodies, Viral
Language	English
Publishing date	2023-05-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12645
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Article ; Online: SARS-CoV-2 variants of concern alpha, beta, gamma and delta have extended ACE2 receptor host ranges.

Thakur, Nazia / Gallo, Giulia / Newman, Joseph / Peacock, Thomas P / Biasetti, Luca / Hall, Catherine N / Wright, Edward / Barclay, Wendy / Bailey, Dalan

The Journal of general virology

2022 Volume 103, Issue 4

Abstract: Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in PR China in late 2019 a number of variants have emerged, with two of these - alpha and delta - subsequently growing to global prevalence. One characteristic of ... ...

Abstract	Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in PR China in late 2019 a number of variants have emerged, with two of these - alpha and delta - subsequently growing to global prevalence. One characteristic of these variants are changes within the spike protein, in particular the receptor-binding domain (RBD). From a public health perspective, these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host range of the virus. Using viral pseudotyping, we examined whether the variants of concern (VOCs) alpha, beta, gamma and delta have differing host angiotensin-converting enzyme 2 (ACE2) receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes that we subsequently attributed to N501Y and E484K substitutions within the spike RBD.
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; Animals ; COVID-19 ; Ferrets ; Host Specificity ; Humans ; Mice ; Peptidyl-Dipeptidase A/chemistry ; Rats ; SARS-CoV-2/genetics
Chemical Substances	Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-04-03
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.0.001735
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Article ; Online: Evaluation of a Live Attenuated Pseudorabies Virus-Vectored Nipah Virus Vaccine

Ashley, Emily C.* / McLean, Rebecca K. / Fuchs, Walter / Klupp, Barbara G. / Thakur, Nazia / Bailey, Dalan / Werling, Dirk M. / Edwards, Jane C. / Mettenleiter, Thomas C. / Graham, Simon P.

[Vortrag]

2023

Keywords	Text ; abstract_or_summary ; ddc:570
Language	English
Publishing date	2023-11-18
Publishing country	de
Document type	Article ; Online
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Article ; Online: An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity.

Wing, Peter A C / Schmidt, Nathalie M / Peters, Rory / Erdmann, Maximilian / Brown, Rachel / Wang, Hao / Swadling, Leo / Newman, Joseph / Thakur, Nazia / Shionoya, Kaho / Morgan, Sophie B / Hinks, Timothy Sc / Watashi, Koichi / Bailey, Dalan / Hansen, Scott B / Davidson, Andrew D / Maini, Mala K / McKeating, Jane A

PLoS pathogens

2023 Volume 19, Issue 5, Page(s) e1011323

Abstract: The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies uncovered a role for ... ...

Abstract	The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 pseudoparticle infection and disrupts the association of ACE2 and GM1 lipid rafts on the cell membrane, perturbing viral attachment. Imaging SARS-CoV-2 RNAs at the single cell level using a viral replicon model identifies the capacity of Avasimibe to limit the establishment of replication complexes required for RNA replication. Genetic studies to transiently silence or overexpress ACAT isoforms confirmed a role for ACAT in SARS-CoV-2 infection. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled during the acute phase of infection. Thus, re-purposing of ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects. Trial registration: NCT04318314.
MeSH term(s)	Humans ; Acyltransferases/antagonists & inhibitors ; Antiviral Agents/pharmacology ; COVID-19 ; SARS-CoV-2 ; T-Lymphocytes
Chemical Substances	Acyltransferases (EC 2.3.-) ; Antiviral Agents ; avasimibe (28LQ20T5RC)
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011323
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Article ; Online: Pseudotyped Bat Coronavirus RaTG13 is efficiently neutralised by convalescent sera from SARS-CoV-2 infected patients

Diego Cantoni / Martin Mayora-Neto / Nazia Thakur / Ahmed M. E. Elrefaey / Joseph Newman / Sneha Vishwanath / Angalee Nadesalingam / Andrew Chan / Peter Smith / Javier Castillo-Olivares / Helen Baxendale / Bryan Charleston / Jonathan Heeney / Dalan Bailey / Nigel Temperton

Communications Biology, Vol 5, Iss 1, Pp 1-

2022 Volume 8

Abstract: Bat Coronavirus RaTG13, a sarbecovirus related to SARS-CoV-2, is more potently neutralized by antibodies from convalescent SARS-CoV-2-infected patients as well as vaccinated healthcare workers despite the spike proteins having high diversity within their ...

Abstract	Bat Coronavirus RaTG13, a sarbecovirus related to SARS-CoV-2, is more potently neutralized by antibodies from convalescent SARS-CoV-2-infected patients as well as vaccinated healthcare workers despite the spike proteins having high diversity within their receptor binding domains (RBD).
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Associations Between Maternal Sociodemographics and Hospital Mortality in Newborns With Prenatally Diagnosed Hypoplastic Left Heart Syndrome.

Lopez, Keila N / Morris, Shaine A / Krishnan, Anita / Jacobs, Marni B / Bhat, Aarti H / Chelliah, Anjali / Chiu, Joanne S / Cuneo, Bettina F / Freire, Grace / Hornberger, Lisa K / Howley, Lisa / Husain, Nazia / Ikemba, Catherine / Kavanaugh-McHugh, Ann / Kutty, Shelby / Lee, Caroline / McBrien, Angela / Michelfelder, Erik C / Pinto, Nelangi M /

Schwartz, Rachel / Stern, Kenan W D / Taylor, Carolyn / Thakur, Varsha / Tworetzky, Wayne / Wittlieb-Weber, Carol / Woldu, Kris / Donofrio, Mary T / Peyvandi, Shabnam

Circulation

2023 Volume 148, Issue 3, Page(s) 283–285

MeSH term(s)	Humans ; Infant, Newborn ; Female ; Pregnancy ; Hypoplastic Left Heart Syndrome ; Hospital Mortality ; Prenatal Diagnosis ; Echocardiography ; Heart Defects, Congenital ; Ultrasonography, Prenatal
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.123.064476
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Article ; Online: Genomic screening of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential.

Tan, Cedric C S / Trew, Jahcub / Peacock, Thomas P / Mok, Kai Yi / Hart, Charlie / Lau, Kelvin / Ni, Dongchun / Orme, C David L / Ransome, Emma / Pearse, William D / Coleman, Christopher M / Bailey, Dalan / Thakur, Nazia / Quantrill, Jessica L / Sukhova, Ksenia / Richard, Damien / Kahane, Laura / Woodward, Guy / Bell, Thomas /

Worledge, Lisa / Nunez-Mino, Joe / Barclay, Wendy / van Dorp, Lucy / Balloux, Francois / Savolainen, Vincent

Nature communications

2023 Volume 14, Issue 1, Page(s) 3322

Abstract: There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. ... ...

Abstract	There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine complete genomes, including two novel coronavirus species, across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk warrants closer surveillance.
MeSH term(s)	Animals ; Humans ; Chiroptera ; COVID-19/genetics ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Genomics ; United Kingdom ; Phylogeny ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-06-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-38717-w
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Article ; Online: Tfh cells and the germinal center are required for memory B cell formation & humoral immunity after ChAdOx1 nCoV-19 vaccination.

Foster, William S / Lee, Jia Le / Thakur, Nazia / Newman, Joseph / Spencer, Alexandra J / Davies, Sophie / Woods, Danielle / Godfrey, Leila / Hay, Iain M / Innocentin, Silvia / Yam-Puc, Juan Carlos / Horner, Emily C / Sharpe, Hayley J / Thaventhiran, James E / Bailey, Dalan / Lambe, Teresa / Linterman, Michelle A

Cell reports. Medicine

2022 Volume 3, Issue 12, Page(s) 100845

Abstract: Emergence from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been facilitated by the rollout of effective vaccines. Successful vaccines generate high-affinity plasma blasts and long-lived protective memory B cells. Here, ... ...

Abstract	Emergence from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been facilitated by the rollout of effective vaccines. Successful vaccines generate high-affinity plasma blasts and long-lived protective memory B cells. Here, we show a requirement for T follicular helper (Tfh) cells and the germinal center reaction for optimal serum antibody and memory B cell formation after ChAdOx1 nCoV-19 vaccination. We found that Tfh cells play an important role in expanding antigen-specific B cells while identifying Tfh-cell-dependent and -independent memory B cell subsets. Upon secondary vaccination, germinal center B cells generated during primary immunizations can be recalled as germinal center B cells again. Likewise, primary immunization GC-Tfh cells can be recalled as either Tfh or Th1 cells, highlighting the pluripotent nature of Tfh cell memory. This study demonstrates that ChAdOx1 nCoV-19-induced germinal centers are a critical source of humoral immunity.
MeSH term(s)	Humans ; Immunity, Humoral ; ChAdOx1 nCoV-19 ; Memory B Cells ; T Follicular Helper Cells ; T-Lymphocytes, Helper-Inducer ; COVID-19/prevention & control ; SARS-CoV-2 ; Germinal Center ; Vaccination ; Immunization, Secondary
Chemical Substances	ChAdOx1 nCoV-19 (B5S3K2V0G8)
Language	English
Publishing date	2022-11-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2022.100845
Database	MEDical Literature Analysis and Retrieval System OnLINE

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