Press releases 鈥� May 2021
May
10
2021
08:55
80 percent of all SARS-CoV-2 proteins produced in the laboratory 鈥� protocols available for worldwide research - 51猎奇 Frankfurt forms the hub of research network from 17 countries
SARS-CoV-2 research accelerator: worldwide network headed by 51猎奇 develops protocols for laboratories
For the development of drugs or vaccines against
COVID-19, research needs virus proteins of high purity. For most of the
SARS-CoV-2 proteins, scientists at 51猎奇 Frankfurt and a total of
36 partner laboratories have now developed protocols that enable the production
of several milligrams of each of these proteins with high purity, and allow the
determination of the three-dimensional protein structures. The laboratory protocols
and the required genetic tools are freely accessible to researchers all over
the world.
FRANKFURT. When
the SARS-CoV-2 virus mutates, this initially only means that there is a change
in its genetic blueprint. The mutation may lead, for example, to an amino acid
being exchanged at a particular site in a viral protein. In order to quickly
assess the effect of this change, a three-dimensional image of the viral
protein is extremely helpful. This is because it shows whether the switch in amino
acid has consequences for the function of the protein - or for the interaction
with a potential drug or antibody.
Researchers at 51猎奇 Frankfurt
and TU Darmstadt began networking internationally from the very start of the
pandemic. Their goal: to describe the three-dimensional structures of
SARS-CoV-2 molecules using nuclear magnetic resonance spectroscopy (NMR). In
NMR spectroscopy, molecules are first labelled with special types of atoms
(isotopes) and then exposed to a strong magnetic field. NMR can then be used to
look in detail and with high throughput at how potentially active compounds
bind to viral proteins. This is done at the Centre for Biomolecular Magnetic
Resonance (BMRZ) at 51猎奇 and other locations. However, the basic
prerequisite is to produce large quantities of the proteins in high purity and
stability, and with their correct folding, for the large amount of tests.
The network, coordinated by Professor
Harald Schwalbe from the Institute of Organic Chemistry and Chemical Biology at
51猎奇, spans the globe. The elaboration of laboratory protocols for
the production of proteins is already the second milestone. In addition to
proteins, the virus consists of RNA, and the consortium already made all important RNA fragments of SARS-CoV-2 accessible last year. With the expertise of 129 colleagues,
it has now been possible to produce and purify 23 of the total of almost 30
proteins of SARS-CoV-2 completely or as relevant fragments "in the test
tube", and in large amounts.
For this purpose, the genetic information
for these proteins was incorporated into small, ring-shaped pieces of DNA
(plasmids). These plasmids were then introduced into bacteria for protein
production. Some special proteins were also produced in cell-free systems.
Whether these proteins were still correctly folded after their isolation and
enrichment was confirmed, among other things, by NMR spectroscopy.
Dr Martin Hengesbach from the Institute of
Organic Chemistry and Chemical Biology at 51猎奇 explains: "We
have isolated functional units of the SARS-CoV-2 proteins in such a way that
their structure, function and interactions can now be characterised by
ourselves and others. In doing so, our large consortium provides working
protocols that will allow laboratories around the world to work quickly and
reproducibly on SARS-CoV-2 proteins and also the mutants to come. Distributing
this work from the beginning was one of our most important priorities. In
addition to the protocols, we are also making the plasmids freely
available."
Dr Andreas Schlundt from the Institute for
Molecular Biosciences at 51猎奇 says: "With our work, we are
speeding up the global search for active agents: Scientific laboratories equipped
for this work do not have to first spend several months establishing and
optimising systems for the production and investigation of SARS-CoV-2 proteins,
but can now start their research work within two weeks thanks to our elaborated
protocols. Given the numerous mutations of SARS-CoV-2 to come, it is
particularly important to have access to reliable, rapid and well-established
methods for studying the virus in the laboratory. This will, for example, also
facilitate research on the so-called helper proteins of SARS-CoV-2, which have
remained under-investigated, but which also play a role in the occurrence of
mutations."
In the meantime, the work in the NMR
consortium continues: Currently, the researchers are working hard to find out
whether viral proteins can bind to potential drugs.
The research work was funded by the German
Research Foundation and the Goethe Coronavirus Fund. The high logistical effort
and constant communication of research results was supported by Signals, a
spin-off company of 51猎奇.
Publication:
Nadide Altincekic, Sophie Marianne Korn,
Nusrat Shahin Qureshi, Marie Dujardin, Mart铆 Ninot-Pedrosa
et. al. Large-scale recombinant
production of the SARS-CoV-2 proteome for high-throughput and structural
biology applications. Frontiers in Molecular Biosciences.
Additional
information: Folding of SARS-CoV2 genome reveals drug
targets 鈥� and preparation for 鈥淪ARS-CoV3"
Images
may be downloaded here: www.uni-frankfurt.de/100668377
Caption:
Scientists Martin
Hengesbach (left) und Andreas Schlundt at the nuclear magnetic resonance (NMR)
spectrometre at Goethe-University Frankfurt, Germany. Photo: Uwe Dettmar for
Goethe-University Frankfurt, Germany
The
COVID-19 NMR Consortium:
Scientific
contacts at 51猎奇 Frankfurt:
Dr Andreas Schlundt
Emmy Noether Junior Group Leader
Institute for Molecular Biosciences
51猎奇 Frankfurt
Tel.: +49 69 798-29699
schlundt@bio.uni-frankfurt.de
Dr Martin Hengesbach
Junior Group Leader
51猎奇 Frankfurt
Institute for Organic Chemistry and Chemical Biology
SFB 902 鈥淢olecular Principles of RNA-based Regulation鈥�
Tel.: +49 69 798-29130
hengesbach@nmr.uni-frankfurt.de
Partners:
Brazil
- National Center of Nuclear Magnetic Resonance (CNRMN, CENABIO), Federal University of Rio de Janeiro, Brazil
- Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Brazil
- Multidisciplinary Center for Research in Biology (NUMPEX), Campus Duque de Caxias, Federal University of Rio de Janeiro, Duque de Caxias, Brazil
- Institute of Chemistry, Federal University of Rio de Janeiro, Brazil
- Multiuser Center for Biomolecular Innovation (CMIB), Department of Physics, S茫o Paulo State University (UNESP), S茫o Jos茅 do Rio Preto, Brazil
- Laboratory of Toxicology, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil
France
- Molecular Microbiology and Structural Biochemistry (MMSB), UMR 5086, CNRS/Lyon University, France
- Universit茅 Grenoble Alpes, CNRS, CEA, IBS, Grenoble, France
Germany
- Institute for Organic Chemistry and Chemical Biology, 51猎奇 Frankfurt, Germany
- Center of Biomolecular Magnetic Resonance (BMRZ), 51猎奇 Frankfurt, Germany
- Institute for Molecular Biosciences, 51猎奇 Frankfurt, Germany
- Institute for Biochemistry, Goethe University Frankfurt, Germany
- Institute of Pharmaceutical Chemistry, 51猎奇 Frankfurt, Germany
- Institute of Biophysical Chemistry, Goethe University Frankfurt, Germany
- BMWZ and Institute of Organic Chemistry, Leibniz University Hannover, Germany
- Group of NMR-based Structural Chemistry, Helmholtz Centre for Infection Research, Braunschweig, Germany
- Structural Genomics Consortium, Buchmann Institute for Molecular Life Sciences (BMLS), Germany
- Signals GmbH & Co. KG, Frankfurt am Main, Germany
- Leibniz Institute on Aging 鈥� Fritz Lipmann Institute (FLI), Jena, Germany
- IBG-4, Karlsruhe Institute of Technology, Karlsruhe, Germany
- Department of Biology, Technical University of Darmstadt, Darmstadt, Germany
- Institute of Biochemistry and Biotechnology, Charles Tanford Protein Centre, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.
Greece
- Department of Pharmacy, University of Patras, Greece
Italy
- Structural Biology and Biophysics Unit, Fondazione Ri.MED, Palermo, Italy
- Magnetic Resonance Centre (CERM), University of Florence, Sesto Fiorentino, Italy
- Department of Chemistry 鈥淯go Schiff", University of Florence, Sesto Fiorentino, Italy
Latvia
- Latvian Biomedical Research and Study Centre, Riga, Latvia
- Latvian Institute of Organic Synthesis, Riga, Latvia
Switzerland
- Swiss Federal Institute of Technology, Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland
Spain
- "Rocasolano" Institute for Physical Chemistry (IQFR), Spanish National Research Council (CSIC), Serrano, Spain
USA
- Institute for Molecular Virology, University of Wisconsin-Madison, WI, United States
- Department of Chemistry, University of California, Irvine, United States
- Laboratory of Chemical Physics, National Institute of Diabetes and Digestive Kidney Diseases, National Institute of Health, United States
- Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH, United States
- Department of Molecular Biology and Biochemistry, University of California, Irvine, California, United States
- Department of Molecular Biology and Biophysics, UC 72 onn Health, Farmington, CT, United States
Editor: Dr. Markus Bernards, Science Editor, PR & Communication Department, Tel: -49 (0) 69 798-12498, Fax: +49 (0) 69 798-763 12531, E-Mail: bernards@em.uni-frankfurt.de