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Nov 23 2020

15:55

Research cooperation between Goethe University, University of Kent and the Hannover Medical School

The drug aprotinin inhibits entry of SARS-CoV2 in host cells

In order for the SARS-CoV2 virus to enter host cells, its “spike" protein has to be cleaved by the cell's own enzymes - proteases. The protease inhibitor aprotinin can prevent cell infection, as scientists at Goethe University, the University of Kent and the Hannover Medical School have now discovered. An aprotinin aerosol is already approved in Russia for the treatment of influenza and could readily be tested for the treatment of COVID-19.

FRANKFURT. The surface of the SARS-CoV-2 virus is studded with spike proteins. The virus needs these in order to dock onto proteins (ACE2 receptors) on the surface of the host cell. Before this docking is possible, parts of the spike protein have to be cleaved by the host cell's enzymes – proteases.

In cell culture experiments with various cell types, the international scientific team led by Professor Jindrich Cinatl, Institute for Medical Virology at the University Hospital Frankfurt, Professor Martin Michaelis, and Dr Mark Wass (both University of Kent) demonstrated that the protease inhibitor aprotinin can inhibit virus replication by preventing SARS-CoV2 entry into host cells. Moreover, aprotinin appears to compensate for a SARS-CoV2-induced reduction of endogenous protease inhibitors in virus-infected cells.

Influenza viruses require host cell proteases for cell entry in a similar way as coronaviruses. Hence, an aprotinin aerosol is already approved in Russia for the treatment of influenza.

Professor Jindrich Cinatl said: “Our findings show that aprotinin is effective against SARS-CoV2 in concentrations that can be achieved in patients. In aprotinin we have a drug candidate for the treatment of COVID-19 that is already approved for other indications and could readily be tested in patients."

Publication: Denisa Bojkova, Marco Bechtel, Katie-May McLaughlin, Jake E. McGreig, Kevin Klann, Carla Bellinghausen, Gernot Rohde, Danny Jonigk, Peter Braubach, Sandra Ciesek, Christian Münch, Mark N. Wass, Martin Michaelis, Jindrich Cinatl jr. Aprotinin inhibits SARS-CoV-2 replication. Cells 2020, https://www.mdpi.com/2073-4409/9/11/2377

Further information:
Professor Dr. rer. nat. Jindrich Cinatl
Institute for Medical Virology
University Hospital Frankfurt am Main
Tel. +49 69 6301-6409
cinatl@em.uni-frankfurt.de
https://www.kgu.de/einrichtungen/institute/zentrum-der-hygiene/medizinische-virologie/forschung/research-group-cinatl/

Nov 20 2020

10:41

Scientists at Goethe University within the international consortium COVID19-NMR refine previous 2D models

Folding of SARS-CoV2 genome reveals drug targets – and preparation for “SARS-CoV3”

For the first time, an international research alliance has observed the RNA folding structures of the SARS-CoV2 genome with which the virus controls the infection process. Since these structures are very similar among various beta corona viruses, the scientists not only laid the foundation for the targeted development of novel drugs for treating COVID-19, but also for future occurrences of infection with new corona viruses that may develop in the future.

FRANKFURT. The genetic code of the SARS-CoV2 virus is exactly 29,902 characters long, strung through a long RNA molecule. It contains the information for the production of 27 proteins. This is not much compared to the possible 40,000 kinds of protein that a human cell can produce. Viruses, however, use the metabolic processes of their host cells to multiply. Crucial to this strategy is that viruses can precisely control the synthesis of their own proteins.

SARS-CoV2 uses the spatial folding of its RNA hereditary molecule as control element for the production of proteins: predominantly in areas that do not code for the viral proteins, RNA single strands adopt structures with RNA double strand sections and loops. However, until now the only models of these foldings have been based on computer analyses and indirect experimental evidence.

Now, an international team of scientists led by chemists and biochemists at Goethe University and TU Darmstadt have experimentally tested the models for the first time. Researchers from the Israeli Weizmann Institute of Science, the Swedish Karolinska Institute and the Catholic University of Valencia were also involved.

The researchers were able to characterise the structure of a total of 15 of these regulatory elements. To do so, they used nuclear magnetic resonance (NMR) spectroscopy in which the atoms of the RNA are exposed to a strong magnetic field, and thereby reveal something about their spatial arrangement. They compared the findings from this method with the findings from a chemical process (dimethyl sulphate footprint) which allows RNA single strand regions to be distinguished from RNA double strand regions.

The coordinator of the consortium, Professor Harald Schwalbe from the Center for Biomolecular Magnetic Resonance at Goethe University Frankfurt, explains: “Our findings have laid a broad foundation for future understanding of how exactly SARS-CoV2 controls the infection process. Scientifically, this was a huge, very labour-intensive effort which we were only able to accomplish because of the extraordinary commitment of the teams here in Frankfurt and Darmstadt together with our partners in the COVID-19-NMR consortium. But the work goes on: together with our partners, we are currently investigating which viral proteins and which proteins of the human host cells interact with the folded regulatory regions of the RNA, and whether this may result in therapeutic approaches."

Worldwide, over 40 working groups with 200 scientists are conducting research within the COVID-19-NMR consortium, including 45 doctoral and postdoctoral students in Frankfurt working in two shifts per day, seven days of the week since the end of March 2020.

Schwalbe is convinced that the potential for discovery goes beyond new therapeutic options for infections with SARS-CoV2: “The control regions of viral RNA whose structure we examined are, for example, almost identical for SARS-CoV and also very similar for other beta-coronaviruses. For this reason, we hope that we can contribute to being better prepared for future 'SARS-CoV3' viruses."

The Center for Biomolecular Magnetic Resonance was founded in 2002 as research infrastructure at Goethe University Frankfurt and has since then received substantial funding from the State of Hessen.

Publication: Anna Wacker, Julia E. Weigand, Sabine R. Akabayov, Nadide Altincekic, Jasleen Kaur Bains, Elnaz Banijamali, Oliver Binas, Jesus Castillo-Martinez, Erhan Cetiner, Betül Ceylan, Liang-Yuan Chiu, Jesse Davila-Calderon, Karthikeyan Dhamotharan, Elke Duchardt-Ferner, Jan Ferner, Lucio Frydman, Boris Fürtig, José Gallego, J. Tassilo Grün, Carolin Hacker, Christina Haddad, Martin Hähnke, Martin Hengesbach, Fabian Hiller, Katharina F. Hohmann, Daniel Hymon, Vanessa de Jesus, Henry Jonker, Heiko Keller, Bozana Knezic, Tom Landgraf, Frank Löhr, Le Luo, Klara R. Mertinkus, Christina Muhs, Mihajlo Novakovic, Andreas Oxenfarth, Martina Palomino-Schätzlein, Katja Petzold, Stephen A. Peter, Dennis J. Pyper, Nusrat S. Qureshi, Magdalena Riad, Christian Richter, Krishna Saxena, Tatjana Schamber, Tali Scherf, Judith Schlagnitweit, Andreas Schlundt, Robbin Schnieders, Harald Schwalbe, Alvaro Simba-Lahuasi, Sridhar Sreeramulu, Elke Stirnal, Alexey Sudakov, Jan-Niklas Tants, Blanton S. Tolbert, Jennifer Vögele, Lena Weiß, Julia Wirmer-Bartoschek, Maria A. Wirtz Martin, Jens Wöhnert, Heidi Zetzsche: Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy. Nucleic Acids Research, 2020, https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkaa1013/5961789

Image download: http://www.uni-frankfurt.de/94413328

Caption: Regulatory RNA elements of the SARS-CoV2 genome. Black: regions not coding for proteins (UTR); orange: coding regions (ORF).

Further information 
Prof. Dr. Harald Schwalbe
 Institute for Chemistry and Chemical Biology  Center for Biomolecular Magnetic Resonance (BMRZ)
 Goethe University Frankfurt
Tel +49 69 798-29137
schwalbe@nmr.uni-frankfurt.de
http://schwalbe.org.chemie.uni-frankfurt.de/

Oct 26 2020

09:21

Film and media scholars at Goethe University Frankfurt dissect the new media world of the pandemic

Of drones, dating-apps and Trump’s COVID strategy

With the onset of the current pandemic, our lives have become more digital and more mediatized than ever before. But how can we understand this transformation, and how can we envision our lives in this “new“ media world? A new publication edited by a group of media scholars working in Frankfurt offers a glimpse of some of the research questions and challenges to come.

FRANKFURT. The current pandemic poses a particular challenge for film and media scholars. COVID-19 changes not just their work routines but transforms their very object of study: the media. “As a consequence of the pandemic, we have to adapt ourselves to new conditions of producing, accessing, consuming, sharing, and deploying media for the flow of information, labor, goods, policies, and culture”, says Laliv Melamed, post-doc researcher in the Graduate Research Training Program “Konfigurationen des Films” (www.konfigurationen-des-films.de). Together with her colleague Phillipp Keidl, Melamed has initiated and co-edited the collection “Pandemic Media”, which appears as an open access publication this week.

“‘Pandemic Media‘ is an attempt to meet the challenges of the pandemic with a series of flashlight essays which address current and future research questions in media studies”, says professor Vinzenz Hediger, project director of “Konfigurationen des Films”. In that spirit, the publication’s subtitles is “Preliminary Notes Towards an Inventory”.

“Pandemic Media“ brings together 37 contributions from the scientific network of “Konfiguration des Films” – a network that is truly global. Contributors include researchers working at universities in New York, Stanford, Toronto, Seattle, Oxford, London, Lagos, Utrecht, Frankfurt, Weimar or Paris. The diversity of the contributors is reflected in the variety of their topics and perspectives: These include the now ubiquitous drone images, the split-screen aesthetics of video conferencing software, dating apps, Trump’s television strategy against COVID, visualisations of the virus or the development and implementation of the COVID tracing app in Germany.

The publication’s cover is based on the current work of MAGNUM photographer Antoine D’Agata, who has been documenting the impact of the pandemic in Paris streets and hospitals with a heat sensor camera. D’Agata’s eerily suggestive images, which are on display at the Brownstone Foundation in Paris until the end of October, are also the subject of one the contributions to the volume.

Among “Pandemic Media”‘s innovations is the digital open access publication strategy, which allowed the editors to put the project in the short space of four months. All contributions underwent a two-step double blind peer review process. The project director of “Konfigurationen des Films“ and Professor Antonio Somaini, who teaches at Université Paris-3 and is also a partner of Goethe University in the International Master Cinema Studies (IMACS, www.imacsite.net) serve as co-editors.

The publication date for the 37 contributions and the introduction is 28 October 2020. “Pandemic Media“ is the latest volume in the „Configurations of film“ series published by meson press. The full publication can be accessed here: https://meson.press/books/pandemic-media/, first in html format, later as PDF files for download. The publication will be available in book form in time for the holidays.

Meson press is an innovative new publisher specializing in open access publications on digital media culture. “From our point of view, ‘Pandemic Media’ is an exciting pilot project”, comments Andreas Kirchner, co-founder and co-director of meson press. “Not only does the volume perfectly fit our profile, it offers us an opportunity to experiment with groundbreaking new publication formats.”

The Graduate Research Training Program “Konfigurationen des Films“, which is funded by the Deutsche Forschungsgemeinschaft (DFG), has been studying the digital transformation of film culture since 2017. This summer, the second cohort of 12 doctoral candidates has assumed their positions and started their research projects.

Publication: „Pandemic Media. Preliminary Notes Towards an Inventory“, published by Vinzenz Hediger, Philipp Keidl, Laliv Melamed und Antonio Somaini

Images to download: http://www.uni-frankfurt.de/93471401

Caption: The temperature of the pandemic: The book cover is based on a photo by Magnum photographer Antoine D’Agata, who has been documenting Parisian street scenes and processes in hospitals with a heat-sensitive camera since April (Foto: Cover (c) meson press/Mathias Bär/Antoine D’Agata)

Further information:

Dr. Philipp Keidl
Graduate Research Training Program „Konfigurationen des Films“
keidl@em.uni-frankfurt.de

Dr. Laliv Melamed,
Graduate Research Training Program „Konfigurationen des Films“
melamed@tfm.uni-frankfurt.de

Prof. Dr. Vinzenz Hediger
Speaker of the Graduate Research Training Program „Konfigurationen des Films“
hediger@tfm.uni-frankfurt.de

Aug 24 2020

14:15

Wastewater provides indication of the degree of infection in population

SARS-CoV-2 viruses in wastewater: monitoring COVID-19 and estimating potential transmission risk

FRANKFURT/AACHEN. Since the beginning of the pandemic, research groups have been working on methods to detect SARS-CoV-2 viruses in wastewater to be used to monitor the degree of COVID-19 transmission among the population. The idea is simple: since infected people shed SARS-CoV-2 viruses in their faeces, wastewater samples could give an indication of the infection numbers among all the residents connected to a wastewater treatment plant. Given sufficient sensitivity, these analyses could function as an early-warning system for authorities, allowing early detection of local case increases within the catchment area of a treatment plant.

A consortium of Frankfurt virologists, ecotoxicologists and evolution researchers, and water researchers from Aachen have now shown for the first time in Germany that SARS-CoV-2 genetic material can be detected in treatment plants using modern molecular methods. Analyses revealed 3 to 20 gene equivalents per millilitre of raw wastewater in all nine treatment plants tested during the first pandemic wave in April 2020. This concentration level was also measured in studies in the Netherlands and the USA.

The researchers were astonished that older retention samples from the years 2017 and 2018, before the outbreak of the pandemic, also delivered signals. Extensive method validation revealed that the gene primer erroneously registered not only SARS-CoV-2, but other non-disease causing coronaviruses in wastewater as well. The current method, developed specifically for SARS-CoV-2 in wastewater, has been confirmed through gene sequencing.

The method can be now employed for what is called wastewater-based epidemiology: the measured viral load of a treatment plant allows conclusions on the number of COVID-19 infected individuals in the catchment area. In the largest treatment plant, 1,037 acute cases were estimated in the catchment area for a viral load of 6 trillion (6 x 1012) gene equivalencies pro day; in smaller treatment plants with viral loads lower by two orders of magnitude, 36 cases were estimated.

The sensitivity is sufficient as an early warning system to indicate whether the action value of 50 incidents per 100,000 residents has been exceeded. Earlier hopes that the precision would be sufficient to determine the estimated number infected people not reported through laboratory diagnosis have not yet been fulfilled. However, the scientists believe that further improvements in the methods are possible.

In vitro cell tests have shown that the SARS-CoV-2 fragments verified in the wastewater are non-infectious. However, due to the high loads and low retention capacity of conventional treatment plants, the behaviour of SARS-CoV-2 in the water cycle should be investigated more deeply. The authors of the study are working on making their knowledge available for an application of the method soon, with the goal of achieving a close cooperation between health ministries, environmental ministries, treatment plant operators and professional associations.

The research team was formed on the initiative of the non-profit Research Institute for Water and Waste Management at RWTH Aachen (FiW), the Institute of Environmental Engineering at RWTH Aachen (ISA), the Institute for Medical Virology at University Hospital Frankfurt (KGU) and Department for Evolution Ecology and Environmental Toxicology at the Institute of Ecology, Evolution and Diversity at Goethe University Frankfurt, and is supported by six water boards in North Rhine-Westphalia, the LOEWE Centre for Translational Biodiversity Genomics (TBG) and the University of Saskatoon in Canada.

Publication: Sandra Westhaus, Frank-Andreas Weber, Sabrina Schiwy, Volker Linnemann, Markus Brinkmann, Marek Widera, Carola Greve, Axel Janke, Henner Hollert, Thomas Wintgens, Sandra Ciesek. Detection of SARS-CoV-2 in raw and treated wastewater in Germany – suitability for COVID-19 surveillance and potential transmission risks. Science of the Total Environment. https://doi.org/10.1016/j.scitotenv.2020.141750, https://www.sciencedirect.com/science/article/pii/S0048969720352797

Further information

University Hospital Frankfurt
Institute for Medical Virology
Prof. Dr. Sandra Ciesek through
University Hospital Frankfurt Press Office
Tel. +49 69 6301 86442
kommunikation@kgu.de

Goethe University Frankfurt
Institute of Ecology, Evolution and Diversity
Dept. Evolution Ecology and Environmental Toxicology
and LOEWE Centre for Translational Biodiversity Genomics (TBG)
Prof. Dr. rer. nat. Henner Hollert
hollert@bio.uni-frankfurt.de

Research Institute for Water and Waste Management at RWTH Aachen (FiW)
Dr. sc. Frank-Andreas Weber
weber@fiw.rwth-aachen.de

RWTH Aachen University
Institute of Environmental Engineering (ISA)
Univ.-Prof. Dr.-Ing. habil. Thomas Wintgens
wintgens@isa.rwth-aachen.de

Aug 20 2020

14:10

78 million for 5-year project for the development of COVID-19 therapies

COVID-19: Goethe University participates in Europe’s largest initiative to accelerate therapy development for COVID-19 and future coronavirus threats

CARE (Corona Accelerated R&D in Europe), supported by Europe’s Innovative Medicines Initiative (IMI), is the largest undertaking of its kind dedicated to discovering and developing urgently needed treatment options for COVID-19. The initiative is committed to a long-term understanding of the disease and development of therapies for COVID-19 and future coronavirus threats in addition to urgent efforts to repurpose existing therapies as potential immediate response. The CARE consortium will accelerate COVID-19 R&D by bringing together the leading expertise and projects of 37 teams from academic and non-profit research institutions and pharmaceutical companies into a comprehensive drug discovery engine.

Complete news release here.

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