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Thesis ; Online: Modelling features of the biological pump and its impact on marine oxygen distribution

Niemeyer, Daniela

2020

Abstract: The marine biological pump not just impacts the uptake of atmospheric CO2 but also contributes to the regulation of ocean dissolved oxygen concentrations. The degree of ocean oxygenation has varied strongly throughout earth’s history. After several ... ...

Abstract	The marine biological pump not just impacts the uptake of atmospheric CO2 but also contributes to the regulation of ocean dissolved oxygen concentrations. The degree of ocean oxygenation has varied strongly throughout earth’s history. After several periods of oxygen depletion, the ocean currently exhibits relatively high oxygen concentrations. However, in the past 50 years, a decrease in oxygen concentrations of 2% in the global ocean has been observed and it is expected that the oxygen concentration will decrease even further with global change conditions, reducing the habitat volume of hypoxia-sensitive pelagic species. Although the interplay between supply of oxygen by ventilation and its consumption by biogeochemical processes is generally known, it is still unclear to which degree both processes influence the global marine oxygen distribution even under today’s climate conditions. Thus, this thesis focuses on features of the biological pump that might impact the marine oxygen distribution. Moreover, a comprehensive understanding of processes that influence the oxygen distribution is important to be able to estimate potential changes under future global change scenarios. Global models are an important tool to get a deeper insight into determinative processes for the marine oxygen distribution. In this thesis, three approaches regarding the biological pump are tested to advance the understanding of processes that determine the oxygen distribution under current climate conditions, which, in turn, potentially enable understanding of the expansion of oxygen minimum zones (OMZs) under future global change conditions: In the second chapter of this thesis, I test two competing feedbacks, which impact future oxygen concentrations, in the University of Victoria Earth System Climate Model (UVic ESCM) of intermediate complexity. This study shows, that the warming-induced phosphorus-oxygen feedback at the sediment-water interface and the resulting potential increase of released phosphorus does not constitute a major ...
Subject code	551
Language	English
Publishing date	2020-08-17
Publishing country	de
Document type	Thesis ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Development of a highly stable, active small interfering RNA with broad activity against SARS-CoV viruses.

Tolksdorf, Beatrice / Heinze, Julian / Niemeyer, Daniela / Röhrs, Viola / Berg, Johanna / Drosten, Christian / Kurreck, Jens

Antiviral research

2024 Volume 226, Page(s) 105879

Abstract: Treatment options for COVID-19 remain limited. Here, we report the optimization of an siRNA targeting the highly conserved leader region of SARS-CoV-2. The siRNA was rendered nuclease resistant by the introduction of modified nucleotides without loss of ... ...

Abstract	Treatment options for COVID-19 remain limited. Here, we report the optimization of an siRNA targeting the highly conserved leader region of SARS-CoV-2. The siRNA was rendered nuclease resistant by the introduction of modified nucleotides without loss of activity. Importantly, the siRNA also retained its inhibitory activity against the emerged omicron sublineage variant BA.2, which occurred after the siRNA was designed and is resistant to other antiviral agents such as antibodies. In addition, we show that a second highly active siRNA designed against the viral 5'-UTR can be applied as a rescue molecule, to minimize the spread of escape mutations. We therefore consider our siRNA-based molecules to be promising broadly active candidates for the treatment of current and future SARS-CoV-2 variants.
Language	English
Publishing date	2024-04-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2024.105879
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Article: SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection

Niemeyer, Daniela / Corman, Victor Max / ZANNAS, ANTHONY / Herrmann, Alexander / Drosten, Christian / Mueller, Marcel / Rein, Theo

Nature Communications, 10:5770

2019

Abstract: Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly- ... ...

Institution	Charité - Universitätsmedizin Berlin Max-Planck-Institut für Psychiatrie (München) Helmholtz Zentrum München Deutsches Zentrum für Infektionsforschung
Abstract	Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.
Keywords	COVID-19 ; Coronavirus ; Antivirals ; MERS-CoV ; Macroautophagy ; Middle East respiratory syndrome coronavirus ; Ubiquitin ligases
Language	English
Document type	Article
Database	Repository for Life Sciences

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Article ; Online: Reduced IFN-ß inhibitory activity of Lagos bat virus phosphoproteins in human compared to Eidolon helvum bat cells.

Papies, Jan / Sieberg, Andrea / Ritz, Daniel / Niemeyer, Daniela / Drosten, Christian / Müller, Marcel A

PloS one

2022 Volume 17, Issue 3, Page(s) e0264450

Abstract: Eidolon helvum bats are reservoir hosts for highly pathogenic lyssaviruses often showing limited disease upon natural infection. An enhanced antiviral interferon (IFN) response combined with reduced inflammation might be linked to the apparent virus ... ...

Abstract	Eidolon helvum bats are reservoir hosts for highly pathogenic lyssaviruses often showing limited disease upon natural infection. An enhanced antiviral interferon (IFN) response combined with reduced inflammation might be linked to the apparent virus tolerance in bats. Lyssavirus phosphoproteins inhibit the IFN response with virus strain-specific efficiency. To date, little is known regarding the lyssavirus P-dependent anti-IFN countermeasures in bats, mainly due to a lack of in vitro tools. By using E. helvum bat cell cultures in a newly established bat-specific IFN-promoter activation assay, we analyzed the IFN-ß inhibitory activity of multiple lyssavirus P in E. helvum compared to human cells. Initial virus infection studies with a recently isolated E. helvum-borne Lagos bat virus street strain from Ghana showed enhanced LBV propagation in an E. helvum lung cell line compared to human A549 lung cells at later time points suggesting effective viral countermeasures against cellular defense mechanisms. A direct comparison of the IFN-ß inhibitory activity of the LBV-GH P protein with other lyssavirus P proteins showed that LBV-GH P and RVP both strongly inhibited the bat IFN-β promotor activation (range 75-90%) in EidLu/20.2 and an E. helvum kidney cell line. Conversely, LBV-GH P blocked the activation of the human IFN-β promoter less efficiently compared to a prototypic Rabies virus P protein (range LBV P 52-68% vs RVP 71-95%) in two different human cell lines (HEK-293T, A549). The same pattern was seen for two prototypic LBV P variants suggesting an overall reduced LBV P IFN-ß inhibitory activity in human cells as compared to E. helvum bat cells. Increased IFN-ß inhibition by lyssavirus P in reservoir host cells might be a result of host-specific adaptation processes towards an enhanced IFN response in bat cells.
MeSH term(s)	Animals ; Antibodies, Viral ; Chiroptera ; Humans ; Interferon-beta ; Lyssavirus ; Nigeria ; Phosphoproteins ; Rhabdoviridae Infections
Chemical Substances	Antibodies, Viral ; Phosphoproteins ; Interferon-beta (77238-31-4)
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0264450
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: High-Sulfated Glycosaminoglycans Prevent Coronavirus Replication.

Möller, Stephanie / Theiß, Janine / Deinert, Thaira I L / Golat, Karoline / Heinze, Julian / Niemeyer, Daniela / Wyrwa, Ralf / Schnabelrauch, Matthias / Bogner, Elke

Viruses

2022 Volume 14, Issue 2

Abstract: Coronaviruses (CoVs) are common among humans and many animals, causing respiratory or gastrointestinal diseases. Currently, only a few antiviral drugs against CoVs are available. Especially for SARS-CoV-2, new compounds for treatment of COVID-19 are ... ...

Abstract	Coronaviruses (CoVs) are common among humans and many animals, causing respiratory or gastrointestinal diseases. Currently, only a few antiviral drugs against CoVs are available. Especially for SARS-CoV-2, new compounds for treatment of COVID-19 are urgently needed. In this study, we characterize the antiviral effects of two high-sulfated glycosaminoglycan (GAG) derivatives against SARS-CoV-2 and bovine coronaviruses (BCoV), which are both members of the Betacoronavirus genus. The investigated compounds are based on hyaluronan (HA) and chondroitin sulfate (CS) and exhibit a strong inhibitory effect against both CoVs. Yield assays were performed using BCoV-infected PT cells in the presence and absence of the compounds. While the high-sulfated HA (sHA3) led to an inhibition of viral growth early after infection, high-sulfated CS (sCS3) had a slightly smaller effect. Time of addition assays, where sHA3 and sCS3 were added to PT cells before, during or after infection, demonstrated an inhibitory effect during all phases of infection, whereas sHA3 showed a stronger effect even after virus absorbance. Furthermore, attachment analyses with prechilled PT cells revealed that virus attachment is not blocked. In addition, sHA3 and sCS3 inactivated BCoV by stable binding. Analysis by quantitative real-time RT PCR underlines the high potency of the inhibitors against BCoV, as well as B.1-lineage, Alpha and Beta SARS-CoV-2 viruses. Taken together, these results demonstrated that the two high-sulfated GAG derivatives exhibit low cytotoxicity and represent promising candidates for an anti-CoV therapy.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; COVID-19/drug therapy ; Cattle ; Cell Line ; Chondroitin Sulfates/chemistry ; Chondroitin Sulfates/pharmacology ; Coronavirus Infections/drug therapy ; Coronavirus Infections/veterinary ; Coronavirus, Bovine/drug effects ; Glycosaminoglycans/chemistry ; Glycosaminoglycans/metabolism ; Glycosaminoglycans/pharmacology ; Humans ; Hyaluronic Acid/chemistry ; Hyaluronic Acid/pharmacology ; SARS-CoV-2/drug effects ; Sulfates/chemistry ; Sulfates/pharmacology ; Virus Attachment/drug effects
Chemical Substances	Antiviral Agents ; Glycosaminoglycans ; Sulfates ; A73025 (268AW7000T) ; Hyaluronic Acid (9004-61-9) ; Chondroitin Sulfates (9007-28-7)
Language	English
Publishing date	2022-02-17
Publishing country	Switzerland
Document type	Journal Article ; 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/v14020413
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online ; Thesis: Modelling features of the biological pump and its impact on marine oxygen distribution

Niemeyer, Daniela [Verfasser] / Kriest, Iris [Akademischer Betreuer] / Schneider, Birgit [Gutachter]

2020

Author's details	Daniela Niemeyer ; Gutachter: Birgit Schneider ; Betreuer: Iris Kriest
Keywords	Naturwissenschaften ; Science
Subject code	sg500
Language	English
Publisher	Universitätsbibliothek Kiel
Publishing place	Kiel
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article: High-Sulfated Glycosaminoglycans Prevent Coronavirus Replication

Möller, Stephanie / Theiß, Janine / Deinert, Thaira I. L. / Golat, Karoline / Heinze, Julian / Niemeyer, Daniela / Wyrwa, Ralf / Schnabelrauch, Matthias / Bogner, Elke

Viruses. 2022 Feb. 17, v. 14, no. 2

2022

Abstract	Coronaviruses (CoVs) are common among humans and many animals, causing respiratory or gastrointestinal diseases. Currently, only a few antiviral drugs against CoVs are available. Especially for SARS-CoV-2, new compounds for treatment of COVID-19 are urgently needed. In this study, we characterize the antiviral effects of two high-sulfated glycosaminoglycan (GAG) derivatives against SARS-CoV-2 and bovine coronaviruses (BCoV), which are both members of the Betacoronavirus genus. The investigated compounds are based on hyaluronan (HA) and chondroitin sulfate (CS) and exhibit a strong inhibitory effect against both CoVs. Yield assays were performed using BCoV-infected PT cells in the presence and absence of the compounds. While the high-sulfated HA (sHA3) led to an inhibition of viral growth early after infection, high-sulfated CS (sCS3) had a slightly smaller effect. Time of addition assays, where sHA3 and sCS3 were added to PT cells before, during or after infection, demonstrated an inhibitory effect during all phases of infection, whereas sHA3 showed a stronger effect even after virus absorbance. Furthermore, attachment analyses with prechilled PT cells revealed that virus attachment is not blocked. In addition, sHA3 and sCS3 inactivated BCoV by stable binding. Analysis by quantitative real-time RT PCR underlines the high potency of the inhibitors against BCoV, as well as B.1-lineage, Alpha and Beta SARS-CoV-2 viruses. Taken together, these results demonstrated that the two high-sulfated GAG derivatives exhibit low cytotoxicity and represent promising candidates for an anti-CoV therapy.
Keywords	Bovine coronavirus ; COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; absorbance ; chondroitin sulfate ; cytotoxicity ; gastrointestinal system ; hyaluronic acid ; therapeutics ; viral growth ; viruses
Language	English
Dates of publication	2022-0217
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14020413
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: SARS-CoV-2 and the safety margins of cell-based biological medicinal products.

Modrof, Jens / Kerschbaum, Astrid / Farcet, Maria R / Niemeyer, Daniela / Corman, Victor M / Kreil, Thomas R

Biologicals : journal of the International Association of Biological Standardization

2020 Volume 68, Page(s) 122–124

Abstract: With the pandemic emergence of SARS-CoV-2, the exposure of cell substrates used for manufacturing of medicines has become a possibility. Cell lines used in biomanufacturing were thus evaluated for their SARS-CoV-2 susceptibility, and the detection of ... ...

Abstract	With the pandemic emergence of SARS-CoV-2, the exposure of cell substrates used for manufacturing of medicines has become a possibility. Cell lines used in biomanufacturing were thus evaluated for their SARS-CoV-2 susceptibility, and the detection of SARS-CoV-2 in culture supernatants by routine adventitious virus testing of fermenter harvest tested.
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Betacoronavirus/physiology ; Biological Factors/pharmacology ; CHO Cells ; COVID-19 ; Chlorocebus aethiops ; Coronavirus Infections/drug therapy ; Coronavirus Infections/metabolism ; Cricetulus ; Drug Evaluation, Preclinical ; HEK293 Cells ; Humans ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/metabolism ; SARS-CoV-2 ; Vero Cells ; Virus Replication
Chemical Substances	Antiviral Agents ; Biological Factors
Keywords	covid19
Language	English
Publishing date	2020-08-29
Publishing country	England
Document type	Journal Article
ZDB-ID	1017370-5
ISSN	1095-8320 ; 1045-1056
ISSN (online)	1095-8320
ISSN	1045-1056
DOI	10.1016/j.biologicals.2020.08.010
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Article ; Online: Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2.

Xie, Qinya / Bozzo, Caterina Prelli / Eiben, Laura / Noettger, Sabrina / Kmiec, Dorota / Nchioua, Rayhane / Niemeyer, Daniela / Volcic, Meta / Lee, Jung-Hyun / Zech, Fabian / Sparrer, Konstantin M J / Drosten, Christian / Kirchhoff, Frank

iScience

2023 Volume 26, Issue 4, Page(s) 106395

Abstract: Opposing effects of interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains poorly ... ...

Abstract	Opposing effects of interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains poorly understood. Here, we demonstrate that endogenous expression of IFITM2 and/or IFITM3 is critical for efficient replication of SARS-CoV-1, SARS-CoV-2 and hCoV-OC43 but has little effect on MERS-, NL63-and 229E-hCoVs. In contrast, overexpression of IFITMs inhibits all these hCoVs, and the corresponding spike-containing pseudo-particles, except OC43, which is enhanced by IFITM3. We further demonstrate that overexpression of IFITMs impairs cell surface expression of ACE2 representing the entry receptor of SARS-CoVs and hCoV-NL63 but not hCoV-OC43. Our results explain the inhibitory effects of artificial IFITM overexpression on ACE2-tropic SARS-CoVs and show that three hCoVs, including major causative agents of severe respiratory disease, hijack IFITMs for efficient infection of human cells.
Language	English
Publishing date	2023-03-13
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106395
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Article ; Online: Hosts and Sources of Endemic Human Coronaviruses.

Corman, Victor M / Muth, Doreen / Niemeyer, Daniela / Drosten, Christian

Advances in virus research

2018 Volume 100, Page(s) 163–188

Abstract: The four endemic human coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 contribute a considerable share of upper and lower respiratory tract infections in adults and children. While their clinical representation resembles that of many other agents of the ...

Abstract	The four endemic human coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 contribute a considerable share of upper and lower respiratory tract infections in adults and children. While their clinical representation resembles that of many other agents of the common cold, their evolutionary histories, and host associations could provide important insights into the natural history of past human pandemics. For two of these viruses, we have strong evidence suggesting an origin in major livestock species while primordial associations for all four viruses may have existed with bats and rodents. HCoV-NL63 and -229E may originate from bat reservoirs as assumed for many other coronaviruses, but HCoV-OC43 and -HKU1 seem more likely to have speciated from rodent-associated viruses. HCoV-OC43 is thought to have emerged from ancestors in domestic animals such as cattle or swine. The bovine coronavirus has been suggested to be a possible ancestor, from which HCoV-OC43 may have emerged in the context of a pandemic recorded historically at the end of the 19th century. New data suggest that HCoV-229E may actually be transferred from dromedary camels similar to Middle East respiratory syndrome (MERS) coronavirus. This scenario provides important ecological parallels to the present prepandemic pattern of host associations of the MERS coronavirus.
MeSH term(s)	Animals ; Coronavirus/classification ; Coronavirus/physiology ; Coronavirus Infections/transmission ; Coronavirus Infections/virology ; Endemic Diseases ; Host Specificity ; Host-Pathogen Interactions ; Humans ; Middle East Respiratory Syndrome Coronavirus/classification ; Middle East Respiratory Syndrome Coronavirus/physiology ; Phylogeny ; Zoonoses/transmission ; Zoonoses/virology
Keywords	covid19
Language	English
Publishing date	2018-02-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	195-8
ISSN	1557-8399 ; 0065-3527
ISSN (online)	1557-8399
ISSN	0065-3527
DOI	10.1016/bs.aivir.2018.01.001
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