Synchrotrons for corona research

Synchrotron light sources were originally built to study particles. Today, they are even used in the fight against COVID-19. The projects are as diverse as the fields of the synchrotron users, who come from universities, research institutions and companies like BioNTech.

To fight COVID-19, we need vaccines and medicine, and to develop these, we need to know the SARS-CoV-2 virus in detail. The virus cannot be seen with a normal light microscope, since it is smaller than the wavelength of visible light. Synchrotrons can produce the short-wave photons or X-rays required. It is of great advantage that we have an outstanding research infrastructure established in the last decades, both in Germany and abroad with German participation. Synchrotron light source facilities include PETRA III and FLASH at the German Electron Synchrotron (DESY) in Hamburg, BESSY II at the Helmholtz Centre Berlin (HZB), European XFEL near Hamburg or ESRF in Grenoble, France. They allow the virus to be imaged with atomic precision.

“The special feature of these large-scale research facilities is that a large community of users can work on their burning questions there. The supply of state-of-the-art methods makes synchrotrons extremely attractive, also and especially for corona research“, says Prof. Dr. Jan-Dierk Grunwaldt (KIT), chair of the German Committee Research with Synchrotron Radiation (KFS).

The heart of a synchrotron is a particle accelerator which accelerates electrons to almost the speed of light. Special magnets deflect the electrons from their trajectory in the synchrotron as they are slowed down, they emit energy in the form of light. These photons, which cover a wide range from infrared to X-ray, are used to study chemical processes, cells and molecules, but also, for example, the spread of aerosol particles or the extent of damage to the lung tissue of COVID patients.

Shortly after the genome of the novel coronavirus SARS-CoV2 was published in early 2020, the first studies started at German synchrotron radiation sources. While synchrotron measurement time normally has to be applied for several months in advance, the synchrotron radiation sources set up a fast-track procedure for coronavirus researchers. They maintained operation for these projects even during the lockdown. This allowed a wide variety of projects to be conducted, for example:

At the beginning of the Corona pandemic, there was little confirmed data on the SARS-CoV-2 virus. Representations were based on low-resolution electron microscopy images or knowledge about the closely related SARS-CoV-1 virus. Now, a team led by biophysicist Dr Andrea Thorn from the University of Hamburg has created a new model of the virus - and is making it publicly available. [more]

Corona virus protease ribbon surface
© H. Tabermann/HZB

In February 2020, the three-dimensional structure of the main protease of the virus was decoded in Berlin by X-ray structural analysis - an important target for drugs against COVID-19. In a project at BESSY II with the universities of Lübeck and Hamburg, possible binding sites and the right structure for drugs are being investigated. One promising substance has already been found. [more]

After the 3D molecular structure of the main protease was known, around 7,000 drugs already approved or undergoing clinical trials were tested at DESY for possible efficacy against the SARS-CoV-2 virus in a large-scale "X-ray screening" in a cooperation between DESY, the Universities of Hamburg and Lübeck, the Bernhard Nocht Institute for Tropical Medicine and Fraunhofer IME. At PETRA III, 37 active substances were identified that bind to the main protease. Two of these active substances are already in the preclinical test phase. [more]

Another large-scale screening of substances that have already been approved for the treatment of other diseases or are in clinical phases has been coordinated by HZB since mid-2021. Together with partners from the Medical University of Innsbruck, Austria, and the University of Olomouc, Czech Republic, the Berlin researchers want to systematically advance drug development. In their NECESSITY project, several viral target proteins are addressed and studied at the MX beamlines of BESSY II. [more]

The Mainz-based company BioNTech, the developer of one of the first Corona vaccines, is conducting research at PETRA III together with university partners to find ways to improve RNA vaccines. [more]

Experts are using PETRA III to look for innovative ways of administering corona drugs with the aim of mitigating possible side effects. [more]

Using the X-ray microscope at BESSY II, a team from Freie Universität Berlin and HZB has succeeded in spatially imaging coronaviruses in cells. They are currently investigating how virus uptake is blocked by clinically approved drugs from the antidepressant group. Antidepressants influence finger-shaped protrusions of the cell, the so-called filopodia. Since the virus also binds to these filopodia, the antidepressants can be used to investigate whether these structures play an important role in the infection.

For the development of drugs, it is important not only to know structures, but also to understand which processes take place. The question of how substances bind to the coronavirus is particularly interesting. Unique insights into these fast processes have been gained by international research collaborations involving DESY at the European XFEL. [more]

Entire lungs of COVID-19 patients were studied at the ESRF as part of a project with the aim to map the entire human body with extremely high resolution (Human Organ Project). The results on lung vessels altered by COVID-19 were published in nature methods in November 2021. Led by the University College London and the ESRF, this work is in cooperation with the Universities Hannover, Heidelberg and Mainz. [more]

At PETRA III, researchers from the University of Göttingen have used an X-ray method originally developed to study brain tissue to examine damaged lung tissue from COVID-19 patients with unprecedented high resolution. The fundamental understanding of the effects of COVID-19 is the basis for better therapies. [more]

A team from the MPI for Chemistry in Mainz and the MPI for Dynamics and Self-Organisation in Göttingen is using microspectroscopy at BESSY II to study the emission and properties of aerosol particles during various activities such as speaking, singing or coughing, in order to better understand their role in the transmission of pathogens. [more]

A new approach to identifying antibodies that neutralise COVID-19 variants has been confirmed at the ESRF's MASSIF-1 beamline in 2021. A collaboration of eight different companies, charities and academic institutions in the UK and France, set up by the UK BioIndustry Association, has publicised this success and hopes to develop drugs from it. [more]

„The fact that these projects were feasible is no coincidence, but the result of consistent and long-term research funding. The fact that we had this research infrastructure in Germany was very fortunate for the fight against the pandemic. Good research simply takes longer than a legislative period.“ says Dr. Andrea Thorn (Uni Hamburg), head of the Coronavirus Structural Task Force and member of the German Committee Research with Synchrotron Radiation (KFS).

The KFS is an elected representation of the more than 4000 users of synchrotron radiation sources in Germany and at international institutions with German participation.

For further information on the various projects, please contact:

KFS press office: Dr. Karin Griewatsch, kfs-presse@sni-portal.de

Oder an:

HZB press office: Dr. Antonia Rötger; Antonia.roetger@helmholtz-berlin.de; Tel: 0049 30 8062-43733

DESY press office: Dr. Thomas Zoufal, thomas.zoufal@desy.de ; Tel.: 49 40 8998-9-1666

ESRF press office: Delphine Chenevier, press@esrf.fr ; Tel.: 33 4 76 88 26 04

European XFEL press office: Dr. Bernd Ebeling, bernd.ebeling@xfel.eu ; Tel: 49 40 8998-6921

Information on corona research in the Helmholtz Association: https://www.helmholtz.de/en/current-topics/coronavirus/

Images:

The coronavirus is studied at synchrotrons like BESSY II at HZB in Berlin. Credit: HZB/Wikimedia Commons

Click on the image for high resolution (2536 x 1687 px)

ESRF scientist Gianluca Santoni, who works on macromolecular crystallography, checks equipment at beamline ID23-1. Credit: ESRF/C. Argoud

Click on the image for high resolution (1021 x 664 px)

DESY researcher Wiebke Ewert shows on a so-called electron density map where a drug candidate (green) binds to the main protease of the corona virus (blue). Credit: DESY/Christian Schmid

Click on the image for high resolution (5197 x 3466 px)