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Article ; Online: Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients.

Giotis, Efstathios S / Cil, Emine / Brooke, Greg N

2022 Volume 14, Issue 12

Abstract: COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or ...

Abstract	COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to become infected by the virus, more likely to develop severe disease and exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and, in particular, androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection, and antiandrogens could be used as a preventative measure at the pre- or early hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19.
MeSH term(s)	Male ; Humans ; Female ; COVID-19 ; SARS-CoV-2/metabolism ; Androgen Antagonists/therapeutic use ; Androgens/physiology ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Antiviral Agents/therapeutic use
Chemical Substances	Androgen Antagonists ; Androgens ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Antiviral Agents
Language	English
Publishing date	2022-12-07
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14122728
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Article ; Online: The antiviral potential of the antiandrogen enzalutamide and the viral-androgen signaling interplay in seasonal coronaviruses.

Ogunjinmi, Oluwadamilola D / Abdullahi, Tukur / Somji, Riaz-Ali / Bevan, Charlotte L / Barclay, Wendy S / Temperton, Nigel / Brooke, Greg N / Giotis, Efstathios S

Journal of medical virology

2024 Volume 96, Issue 3, Page(s) e29540

Abstract: The sex disparity in COVID-19 outcomes with males generally faring worse than females has been associated with the androgen-regulated expression of the protease TMPRSS2 and the cell receptor ACE2 in the lung and fueled interest in antiandrogens as ... ...

Abstract	The sex disparity in COVID-19 outcomes with males generally faring worse than females has been associated with the androgen-regulated expression of the protease TMPRSS2 and the cell receptor ACE2 in the lung and fueled interest in antiandrogens as potential antivirals. In this study, we explored enzalutamide, an antiandrogen used commonly to treat prostate cancer, as a potential antiviral against the human coronaviruses which cause seasonal respiratory infections (HCoV-NL63, -229E, and -OC43). Using lentivirus-pseudotyped and authentic HCoV, we report that enzalutamide reduced 229E and NL63 entry and infection in both TMPRSS2- and nonexpressing immortalized cells, suggesting a TMPRSS2-independent mechanism. However, no effect was observed against OC43. To decipher this distinction, we performed RNA-sequencing analysis on 229E- and OC43-infected primary human airway cells. Our results show a significant induction of androgen-responsive genes by 229E compared to OC43 at 24 and 72 h postinfection. The virus-mediated effect on AR-signaling was further confirmed with a consensus androgen response element-driven luciferase assay in androgen-depleted MRC-5 cells. Specifically, 229E induced luciferase-reporter activity in the presence and absence of the synthetic androgen mibolerone, while OC43 inhibited induction. These findings highlight a complex interplay between viral infections and androgen-signaling, offering insights for disparities in viral outcomes and antiviral interventions.
MeSH term(s)	Male ; Female ; Humans ; Androgens/metabolism ; Androgens/pharmacology ; Androgen Antagonists/pharmacology ; Androgen Antagonists/metabolism ; Seasons ; Coronavirus 229E, Human ; Antiviral Agents/pharmacology ; Antiviral Agents/metabolism ; Luciferases ; Benzamides ; Nitriles ; Phenylthiohydantoin
Chemical Substances	Androgens ; enzalutamide (93T0T9GKNU) ; Androgen Antagonists ; Antiviral Agents ; Luciferases (EC 1.13.12.-) ; Benzamides ; Nitriles ; Phenylthiohydantoin (2010-15-3)
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.29540
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Article ; Online: Structural and functional modelling of SARS-CoV-2 entry in animal models.

Brooke, Greg N / Prischi, Filippo

Scientific reports

2020 Volume 10, Issue 1, Page(s) 15917

Abstract: SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, ... ...

Abstract	SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.
MeSH term(s)	Amino Acid Sequence/genetics ; Angiotensin-Converting Enzyme 2 ; Animals ; Betacoronavirus/genetics ; COVID-19 ; Cats ; Computational Biology/methods ; Coronavirus Infections/pathology ; Coronavirus Infections/veterinary ; Cricetinae ; Disease Models, Animal ; Dogs ; Ferrets ; Furin/genetics ; Furin/metabolism ; Guinea Pigs ; Humans ; Macaca fascicularis ; Mice ; Molecular Docking Simulation ; Pandemics/veterinary ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/pathology ; Pneumonia, Viral/veterinary ; Rabbits ; Rats ; SARS-CoV-2 ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Ace2 protein, mouse (EC 3.4.17.23) ; Ace2 protein, rat (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; Furin (EC 3.4.21.75)
Keywords	covid19
Language	English
Publishing date	2020-09-28
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/s41598-020-72528-z
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Article ; Online: PSIP1/LEDGF reduces R-loops at transcription sites to maintain genome integrity.

Jayakumar, Sundarraj / Patel, Manthan / Boulet, Fanny / Aziz, Hadicha / Brooke, Greg N / Tummala, Hemanth / Pradeepa, Madapura M

Nature communications

2024 Volume 15, Issue 1, Page(s) 361

Abstract: R-loops that accumulate at transcription sites pose a persistent threat to genome integrity. PSIP1 is a chromatin protein associated with transcriptional elongation complex, possesses histone chaperone activity, and is implicated in recruiting RNA ... ...

Abstract	R-loops that accumulate at transcription sites pose a persistent threat to genome integrity. PSIP1 is a chromatin protein associated with transcriptional elongation complex, possesses histone chaperone activity, and is implicated in recruiting RNA processing and DNA repair factors to transcription sites. Here, we show that PSIP1 interacts with R-loops and other proteins involved in R-loop homeostasis, including PARP1. Genome-wide mapping of PSIP1, R-loops and γ-H2AX in PSIP1-depleted human and mouse cell lines revealed an accumulation of R-loops and DNA damage at gene promoters in the absence of PSIP1. R-loop accumulation causes local transcriptional arrest and transcription-replication conflict, leading to DNA damage. PSIP1 depletion increases 53BP1 foci and reduces RAD51 foci, suggesting altered DNA repair choice. Furthermore, PSIP1 depletion increases the sensitivity of cancer cells to PARP1 inhibitors and DNA-damaging agents that induce R-loop-induced DNA damage. These findings provide insights into the mechanism through which PSIP1 maintains genome integrity at the site of transcription.
MeSH term(s)	Humans ; Animals ; Mice ; R-Loop Structures/genetics ; Intercellular Signaling Peptides and Proteins ; Cell Line ; DNA Damage ; Transcription Factors/genetics ; Adaptor Proteins, Signal Transducing
Chemical Substances	lens epithelium-derived growth factor ; Intercellular Signaling Peptides and Proteins ; PSIP1 protein, human ; Transcription Factors ; Adaptor Proteins, Signal Transducing
Language	English
Publishing date	2024-01-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44544-w
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Article ; Online: Structural and functional modelling of SARS-CoV-2 entry in animal models

Greg N. Brooke / Filippo Prischi

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 11

Abstract: Abstract SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective ... ...

Abstract	Abstract SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.
Keywords	Medicine ; R ; Science ; Q ; covid19
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: PSIP1/LEDGF reduces R-loops at transcription sites to maintain genome integrity

Sundarraj Jayakumar / Manthan Patel / Fanny Boulet / Hadicha Aziz / Greg N. Brooke / Hemanth Tummala / Madapura M. Pradeepa

Nature Communications, Vol 15, Iss 1, Pp 1-

2024 Volume 14

Abstract: Abstract R-loops that accumulate at transcription sites pose a persistent threat to genome integrity. PSIP1 is a chromatin protein associated with transcriptional elongation complex, possesses histone chaperone activity, and is implicated in recruiting ... ...

Abstract	Abstract R-loops that accumulate at transcription sites pose a persistent threat to genome integrity. PSIP1 is a chromatin protein associated with transcriptional elongation complex, possesses histone chaperone activity, and is implicated in recruiting RNA processing and DNA repair factors to transcription sites. Here, we show that PSIP1 interacts with R-loops and other proteins involved in R-loop homeostasis, including PARP1. Genome-wide mapping of PSIP1, R-loops and γ-H2AX in PSIP1-depleted human and mouse cell lines revealed an accumulation of R-loops and DNA damage at gene promoters in the absence of PSIP1. R-loop accumulation causes local transcriptional arrest and transcription-replication conflict, leading to DNA damage. PSIP1 depletion increases 53BP1 foci and reduces RAD51 foci, suggesting altered DNA repair choice. Furthermore, PSIP1 depletion increases the sensitivity of cancer cells to PARP1 inhibitors and DNA-damaging agents that induce R-loop-induced DNA damage. These findings provide insights into the mechanism through which PSIP1 maintains genome integrity at the site of transcription.
Keywords	Science ; Q
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Roles of steroid receptors in the lung and COVID-19.

Leach, Damien A / Brooke, Greg N / Bevan, Charlotte L

Essays in biochemistry

2021 Volume 65, Issue 6, Page(s) 1025–1038

Abstract: COVID-19 symptoms and mortality are largely due to its devastating effects in the lungs. The disease is caused by the SARS (Severe Acute Respiratory Syndrome)-CoV-2 coronavirus, which requires host cell proteins such as ACE2 (angiotensin-converting ... ...

Abstract	COVID-19 symptoms and mortality are largely due to its devastating effects in the lungs. The disease is caused by the SARS (Severe Acute Respiratory Syndrome)-CoV-2 coronavirus, which requires host cell proteins such as ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) for infection of lung epithelia. The expression and function of the steroid hormone receptor family is important in many aspects that impact on COVID-19 effects in the lung - notably lung development and function, the immune system, and expression of TMPRSS2 and ACE2. This review provides a brief summary of current knowledge on the roles of the steroid hormone receptors [androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), mineralocorticoid receptor (MR) and oestrogen receptor (ER)] in the lung, their effects on host cell proteins that facilitate SARS-CoV-2 uptake, and provides a snapshot of current clinical trials investigating the use of steroid receptor (SR) ligands to treat COVID-19.
MeSH term(s)	Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/metabolism ; COVID-19/virology ; Female ; Hormone Antagonists/therapeutic use ; Humans ; Immunomodulation ; Lung/metabolism ; Lung/virology ; Male ; Receptors, Androgen/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Glucocorticoid/metabolism ; Receptors, Mineralocorticoid/metabolism ; Receptors, Progesterone/metabolism ; Receptors, Steroid/metabolism ; SARS-CoV-2 ; Serine Endopeptidases/metabolism ; Sex Factors ; COVID-19 Drug Treatment
Chemical Substances	Hormone Antagonists ; Receptors, Androgen ; Receptors, Estrogen ; Receptors, Glucocorticoid ; Receptors, Mineralocorticoid ; Receptors, Progesterone ; Receptors, Steroid ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Language	English
Publishing date	2021-07-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1744-1358 ; 0071-1365
ISSN (online)	1744-1358
ISSN	0071-1365
DOI	10.1042/EBC20210005
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Article ; Online: The role of the p90 ribosomal S6 kinase family in prostate cancer progression and therapy resistance.

Cronin, Ryan / Brooke, Greg N / Prischi, Filippo

Oncogene

2021 Volume 40, Issue 22, Page(s) 3775–3785

Abstract: Prostate cancer (PCa) is the second most commonly occurring cancer in men, with over a million new cases every year worldwide. Tumor growth and disease progression is mainly dependent on the Androgen Receptor (AR), a ligand dependent transcription factor. ...

Abstract	Prostate cancer (PCa) is the second most commonly occurring cancer in men, with over a million new cases every year worldwide. Tumor growth and disease progression is mainly dependent on the Androgen Receptor (AR), a ligand dependent transcription factor. Standard PCa therapeutic treatments include androgen-deprivation therapy and AR signaling inhibitors. Despite being successful in controlling the disease in the majority of men, the high frequency of disease progression to aggressive and therapy resistant stages (termed castrate resistant prostate cancer) has led to the search for new therapeutic targets. The p90 ribosomal S6 kinase (RSK1-4) family is a group of highly conserved Ser/Thr kinases that holds promise as a novel target. RSKs are effector kinases that lay downstream of the Ras/Raf/MEK/ERK signaling pathway, and aberrant activation or expression of RSKs has been reported in several malignancies, including PCa. Despite their structural similarities, RSK isoforms have been shown to perform nonredundant functions and target a wide range of substrates involved in regulation of transcription and translation. In this article we review the roles of the RSKs in proliferation and motility, cell cycle control and therapy resistance in PCa, highlighting the possible interplay between RSKs and AR in mediating disease progression. In addition, we summarize the current advances in RSK inhibitor development and discuss their potential clinical benefits.
MeSH term(s)	Androgen Antagonists/therapeutic use ; Humans ; MAP Kinase Signaling System ; Male ; Phosphorylation ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/enzymology ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/enzymology ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Prostatic Neoplasms, Castration-Resistant/pathology ; Receptors, Androgen/metabolism ; Ribosomal Protein S6 Kinases, 90-kDa/metabolism ; Signal Transduction
Chemical Substances	AR protein, human ; Androgen Antagonists ; Receptors, Androgen ; Ribosomal Protein S6 Kinases, 90-kDa (EC 2.7.11.1)
Language	English
Publishing date	2021-05-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-021-01810-9
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Article ; Online: Structural and functional modelling of SARS-CoV-2 entry in animal models

Brooke, Greg N. / Prischi, Filippo

Scientific Reports

2020 Volume 10, Issue 1

Abstract	Abstract SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.
Keywords	Multidisciplinary ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	2615211-3
ISSN	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-72528-z
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Article: Structural and functional modelling of SARS-CoV-2 entry in animal models

Brooke, Greg N / Prischi, Filippo

Sci Rep

Abstract	SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #800800
Database	COVID19

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