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Article: SARS-CoV-2-host cell surface interactions and potential antiviral therapies.

Butnariu, Aura-Bianca / Look, Alex / Grillo, Marta / Tabish, Tanveer A / McGarvey, Michael J / Pranjol, Md Zahidul I

Interface focus

2021 Volume 12, Issue 1, Page(s) 20200081

Abstract: In this review, we reveal the latest developments at the interface between SARS-CoV-2 and the host cell surface. In particular, we evaluate the current and potential mechanisms of binding, fusion and the conformational changes of the spike (S) protein to ...

Abstract	In this review, we reveal the latest developments at the interface between SARS-CoV-2 and the host cell surface. In particular, we evaluate the current and potential mechanisms of binding, fusion and the conformational changes of the spike (S) protein to host cell surface receptors, especially the human angiotensin-converting enzyme 2 (ACE2) receptor. For instance, upon the initial attachment, the receptor binding domain of the S protein forms primarily hydrogen bonds with the protease domain of ACE2 resulting in conformational changes within the secondary structure. These surface interactions are of paramount importance and have been therapeutically exploited for antiviral design, such as monoclonal antibodies. Additionally, we provide an insight into novel therapies that target viral non-structural proteins, such as viral RNA polymerase. An example of which is remdesivir which has now been approved for use in COVID-19 patients by the US Food and Drug Administration. Establishing further understanding of the molecular details at the cell surface will undoubtably aid the development of more efficacious and selectively targeted therapies to reduce the burden of COVID-19.
Language	English
Publishing date	2021-12-10
Publishing country	England
Document type	Journal Article ; Review
ISSN	2042-8898
ISSN	2042-8898
DOI	10.1098/rsfs.2020.0081
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination.

Fumagalli, Valeria / Ravà, Micol / Marotta, Davide / Di Lucia, Pietro / Bono, Elisa B / Giustini, Leonardo / De Leo, Federica / Casalgrandi, Maura / Monteleone, Emanuele / Mouro, Violette / Malpighi, Chiara / Perucchini, Chiara / Grillo, Marta / De Palma, Sara / Donnici, Lorena / Marchese, Silvia / Conti, Matteo / Muramatsu, Hiromi / Perlman, Stanley /

Pardi, Norbert / Kuka, Mirela / De Francesco, Raffaele / Bianchi, Marco E / Guidotti, Luca G / Iannacone, Matteo

Nature immunology

2024 Volume 25, Issue 4, Page(s) 633–643

Abstract: Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under ... ...

Abstract	Vaccines have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality, yet emerging variants challenge their effectiveness. The prevailing approach to updating vaccines targets the antibody response, operating under the presumption that it is the primary defense mechanism following vaccination or infection. This perspective, however, can overlook the role of T cells, particularly when antibody levels are low or absent. Here we show, through studies in mouse models lacking antibodies but maintaining functional B cells and lymphoid organs, that immunity conferred by prior infection or mRNA vaccination can protect against SARS-CoV-2 challenge independently of antibodies. Our findings, using three distinct models inclusive of a novel human/mouse ACE2 hybrid, highlight that CD8
MeSH term(s)	Humans ; Animals ; Mice ; SARS-CoV-2 ; CD8-Positive T-Lymphocytes ; COVID-19/prevention & control ; Antibodies ; Vaccination ; Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	Antibodies ; Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-024-01787-z
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 42: Show issues

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Article: Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets.

Alard, Emilie / Butnariu, Aura-Bianca / Grillo, Marta / Kirkham, Charlotte / Zinovkin, Dmitry Aleksandrovich / Newnham, Louise / Macciochi, Jenna / Pranjol, Md Zahidul Islam

Cancers

2020 Volume 12, Issue 7

Abstract: Unlike traditional cancer therapies, such as surgery, radiation and chemotherapy that are typically non-specific, cancer immunotherapy harnesses the high specificity of a patient's own immune system to selectively kill cancer cells. The immune system is ... ...

Abstract	Unlike traditional cancer therapies, such as surgery, radiation and chemotherapy that are typically non-specific, cancer immunotherapy harnesses the high specificity of a patient's own immune system to selectively kill cancer cells. The immune system is the body's main cancer surveillance system, but cancers may evade destruction thanks to various immune-suppressing mechanisms. We therefore need to deploy various immunotherapy-based strategies to help bolster the anti-tumour immune responses. These include engineering T cells to express chimeric antigen receptors (CARs) to specifically recognise tumour neoantigens, inactivating immune checkpoints, oncolytic viruses and dendritic cell (DC) vaccines, which have all shown clinical benefit in certain cancers. However, treatment efficacy remains poor due to drug-induced adverse events and immunosuppressive tendencies of the tumour microenvironment. Recent preclinical studies have unveiled novel therapies such as anti-cathepsin antibodies, galectin-1 blockade and anti-OX40 agonistic antibodies, which may be utilised as adjuvant therapies to modulate the tumour microenvironment and permit more ferocious anti-tumour immune response.
Keywords	covid19
Language	English
Publishing date	2020-07-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12071826
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Article ; Online: Administration of aerosolized SARS-CoV-2 to K18-hACE2 mice uncouples respiratory infection from fatal neuroinvasion.

Science immunology

2022 Volume 7, Issue 67, Page(s) eabl9929

Abstract: The development of a tractable small animal model faithfully reproducing human coronavirus disease 2019 pathogenesis would arguably meet a pressing need in biomedical research. Thus far, most investigators have used transgenic mice expressing the human ... ...

Abstract	The development of a tractable small animal model faithfully reproducing human coronavirus disease 2019 pathogenesis would arguably meet a pressing need in biomedical research. Thus far, most investigators have used transgenic mice expressing the human ACE2 in epithelial cells (K18-hACE2 transgenic mice) that are intranasally instilled with a liquid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suspension under deep anesthesia. Unfortunately, this experimental approach results in disproportionate high central nervous system infection leading to fatal encephalitis, which is rarely observed in humans and severely limits this model’s usefulness. Here, we describe the use of an inhalation tower system that allows exposure of unanesthetized mice to aerosolized virus under controlled conditions. Aerosol exposure of K18-hACE2 transgenic mice to SARS-CoV-2 resulted in robust viral replication in the respiratory tract, anosmia, and airway obstruction but did not lead to fatal viral neuroinvasion. When compared with intranasal inoculation, aerosol infection resulted in a more pronounced lung pathology including increased immune infiltration, fibrin deposition, and a transcriptional signature comparable to that observed in SARS-CoV-2–infected patients. This model may prove useful for studies of viral transmission, disease pathogenesis (including long-term consequences of SARS-CoV-2 infection), and therapeutic interventions.
MeSH term(s)	Administration, Inhalation ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; COVID-19/immunology ; COVID-19/physiopathology ; COVID-19/virology ; Disease Models, Animal ; Encephalitis, Viral/mortality ; Encephalitis, Viral/prevention & control ; Epithelial Cells/metabolism ; Female ; Humans ; Keratin-18/genetics ; Keratin-18/metabolism ; Lung/immunology ; Lung/pathology ; Lung/physiopathology ; Male ; Mice ; Mice, Transgenic ; Nasal Sprays ; Promoter Regions, Genetic/genetics ; SARS-CoV-2/physiology ; Transcriptome ; Virus Replication
Chemical Substances	Keratin-18 ; Nasal Sprays ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abl9929
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Article ; Online: Group 1 ILCs regulate T cell-mediated liver immunopathology by controlling local IL-2 availability.

Science immunology

2022 Volume 7, Issue 68, Page(s) eabi6112

Abstract: Group 1 innate lymphoid cells (ILCs), which comprise both natural killer (NK) cells and ILC1s, are important innate effectors that can also positively and negatively influence adaptive immune responses. The latter function is generally ascribed to the ... ...

Abstract	Group 1 innate lymphoid cells (ILCs), which comprise both natural killer (NK) cells and ILC1s, are important innate effectors that can also positively and negatively influence adaptive immune responses. The latter function is generally ascribed to the ability of NK cells to recognize and kill activated T cells. Here, we used multiphoton intravital microscopy in mouse models of hepatitis B to study the intrahepatic behavior of group 1 ILCs and their cross-talk with hepatitis B virus (HBV)-specific CD8
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Immunity, Innate/immunology ; Interleukin-2/immunology ; Killer Cells, Natural/immunology ; Lymphocytes/immunology ; Mice ; Mice, Congenic ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic
Chemical Substances	Interleukin-2
Language	English
Publishing date	2022-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abi6112
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Controlled administration of aerosolized SARS-CoV-2 to K18-hACE2 transgenic mice uncouples respiratory infection and anosmia from fatal neuroinvasion

bioRxiv

Abstract: The development of a tractable small animal model faithfully reproducing human COVID-19 pathogenesis would arguably meet a pressing need in biomedical research. Thus far, most investigators have used transgenic mice expressing the human ACE2 in ... ...

Abstract	The development of a tractable small animal model faithfully reproducing human COVID-19 pathogenesis would arguably meet a pressing need in biomedical research. Thus far, most investigators have used transgenic mice expressing the human ACE2 in epithelial cells (K18-hACE2 transgenic mice) that are intranasally instilled with a liquid SARS-CoV-2 suspension under deep anesthesia. Unfortunately, this experimental approach results in disproportionate high CNS infection leading to fatal encephalitis, which is rarely observed in humans and severely limits this model9s usefulness. Here, we describe the use of an inhalation tower system that allows exposure of unanesthetized mice to aerosolized virus under controlled conditions. Aerosol exposure of K18-hACE2 transgenic mice to SARS-CoV-2 resulted in robust viral replication in the respiratory tract, anosmia, and airway obstruction, but did not lead to fatal viral neuroinvasion. When compared to intranasal inoculation, aerosol infection resulted in a more pronounced lung pathology including increased immune infiltration, fibrin deposition and a transcriptional signature comparable to that observed in SARS-CoV-2-infected patients. This model may prove useful for studies of viral transmission, disease pathogenesis (including long-term consequences of SARS-CoV-2 infection) and therapeutic interventions.
Keywords	covid19
Language	English
Publishing date	2021-08-06
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.08.06.455382
Database	COVID19

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Article: SARS-CoV-2-host cell surface interactions and potential antiviral therapies.

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Article ; Online: Antibody-independent protection against heterologous SARS-CoV-2 challenge conferred by prior infection or vaccination.

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Article: Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets.

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Article ; Online: Administration of aerosolized SARS-CoV-2 to K18-hACE2 mice uncouples respiratory infection from fatal neuroinvasion.

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Article ; Online: Group 1 ILCs regulate T cell-mediated liver immunopathology by controlling local IL-2 availability.

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Article ; Online: Controlled administration of aerosolized SARS-CoV-2 to K18-hACE2 transgenic mice uncouples respiratory infection and anosmia from fatal neuroinvasion

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Inter-library loan at ZB MED