Tag: SARS-CoV-2

Universal vaccine of the future

Universal vaccine of the future

Researchers from the Małopolska Centre of Biotechnology have developed an innovative, modular nanoparticle that could become the foundation of a universal vaccine. By using a phage capsid and antigens derived from the SARS-CoV-2 virus, along with immune response-enhancing elements, the new technology allows for rapid adaptation of the vaccine to emerging pathogens. The structural part of the project was carried out at the Cryo-Electron Microscopy Laboratory at the National Synchrotron Radiation Centre SOLARIS.

Researchers have developed a nanoparticle is based on a phage capsid that has been devoid of its own genetic material and instead equipped with antigens derived from the SARS-CoV-2 virus: specifically, the RBD (Receptor Binding Domain) protein. The research team, led by Dr. Antonina Naskalska, enhanced the nanoparticles with elements that could potentially boost the immune response: short, single-stranded DNA fragments or longer, coding mRNA sequences. The nanoparticle was designed in a modular fashion, allowing for the replacement of antigens displayed on its surface or molecules packed inside the capsid. The advantage of such a vaccine design lies in its ability to be rapidly adapted to an emerging pathogen or a new virus variant.


One of the key aspects of the presented vaccine prototype is the trimeric form of the RBD protein—identical to the form found in the SARS-CoV-2 virus. An organism vaccinated with such an antigen has a greater chance of producing effective antibodies that, in the event of exposure to the virus, will protect it from infection. Demonstrating the trimeric form of the RBD antigen on the surface of the presented nanoparticles was made possible through structural studies using cryogenic electron microscopy (cryo-EM), conducted at the National Synchrotron Radiation Centre SOLARIS.

Read more on SOLARIS website

Industrial clients at ESRF fast-track drug discovery

Industrial clients at ESRF fast-track drug discovery

Researchers from the company Idorsia Pharmaceuticals Ltd have rapidly optimized a weak hit compound against SARS-CoV-2 to increase its potency by 1000-fold. They used artificial intelligence, computational chemistry, high throughput chemistry and structural biology at the ESRF. The results are out in Journal of Medicinal Chemistry and show the strong collaboration between the ESRF and industry.

It all started with a molecule that bound weakly to the SARS-CoV-2, the virus responsible for COVID-19. “About two year ago, we had identified this molecule, a diazepane scaffold, through artificial intelligence and computational screening and thought we would investigate further”, explains Julien Hazemann, first author of the publication and former researcher at Idorsia. The compound could potentially inhibit the virus’s main protease (Mpro)—a critical enzyme for viral replication.

In order to increase the efficiency of the molecule, so that it would bind to Mpro, the team from Idorsia used computational simulations, high-throughput chemistry and structural biology at the ESRF in collaboration with the company Expose GmbH. This approach, called hit-to-lead optimisation, has been used in antiviral drug discovery in the last ten years, but it is the first time that the techniques were integrated in such a tight and effective way in a global effort.  

First, the researchers employed computational docking and molecular dynamics simulations to predict how structural changes to the molecule might improve binding to Mpro.

Using high-throughput medicinal chemistry, they synthesized and tested a focused library of analogues. These steps led to a dramatic improvement of the original compound to a nearly 1,000-fold increase in potency.

However, predicting how a molecule behaves computationally was only one piece of the puzzle. Throughout the process, the researchers came to the ESRF’s macromolecular crystallography beamline ID23-1 to collect high-resolution X-ray diffraction data of the Mpro–inhibitor complexes. They were able to visualise how the inhibitor binds within the active site of the protease. “The ESRF has been crucial in this research, from the beginning, when we scanned the candidate compound, to the end, when we saw how the action takes place”, explains Daniel Ritz, senior director of biology at Idorsia.

One of the features of this study is the small number of compounds they needed, thanks to the highly targeted methodology the scientists used.

Read more on ESRF website

Striking structural similarities in RNA of four Betacoronaviruses

Striking structural similarities in RNA of four Betacoronaviruses

In a study published in Nucleic Acids Research, a team from the International Institute of Molecular and Cell Biology in Warsaw (IIMCB), led by Prof. Janusz Bujnicki, in collaboration with the Spanish National Research Council (CSIC) in Madrid and the Jagiellonian University in Krakow, made a significant discovery regarding the four main types of betacoronaviruses, including the deadly viruses SARS-CoV-2 and MERS, as well as the OC43 virus that causes colds. The research was carried out using the research infrastructure of the SOLARIS National Synchrotron Radiation Centre.

The scientists analyzed the ribonucleic acid (RNA) molecules – the genetic material of betacoronaviruses. The RNA nucleotide sequences of coronaviruses, which are about 30,000 nucleotides long, differ significantly from each other. In this work, detailed analyses focused on examining the spatial structure and dynamics of about 500 nucleotides at the very beginning of the viral RNA (the “5′ end”), which plays a crucial role in the replication of viruses in infected cells.

The 5′ ends of the genomic RNA of four different coronaviruses were examined using advanced biochemical, biophysical, and bioinformatics techniques, including chemical probing, cryo-electron microscopy, atomic force microscopy, and computer modeling. The results revealed the presence of very similar structural elements, despite being formed by different nucleotide sequences in the RNA of various betacoronaviruses.

“This discovery is fundamental for understanding the similarities in the functioning of betacoronaviruses,” says Prof. Janusz Bujnicki from the IIMCB, the project leader. “The spatial structures we have identified in the RNA molecules of viruses may contribute to the development of new antiviral drugs in the future.”

The significance of the published discovery goes beyond understanding the SARS-CoV-2 virus responsible for the COVID-19 pandemic and sheds new light on the molecular mechanisms of how all coronaviruses function.

This research was possible thanks to the international collaboration of scientists from Warsaw, Krakow, and Madrid. The project was initiated as part of the COVID-19 research program, funded by the National Science Centre (grant 2020/01/0/NZ1/00232), and then continued with support from other national and international sources. Key to success was the effective cooperation of experts from various fields of science.

Read more on SOLARIS website

Image: Evolutionarily conserved structures of SL5 regulatory elements in Betacoronavirus RNA genomes

Finding the chink in corona’s armour

Finding the chink in corona’s armour

The COVID-19 pandemic resulted in millions of deaths. Despite an unparalleled collaborative research effort that led to effective vaccines and therapies being produced in record-breaking time, a complete understanding of the structure and lifecycle of the coronavirus known as SARS-CoV-2 is still lacking. Scientists used the biolabs and the SPB/SFX instrument at the European XFEL to study the main protease, or Mpro, of the virus to understand how it protects itself from oxidative damage. The results add key knowledge to our understanding of the workings of SARS-CoV-2 and the field of viral biology.

Between January 2020 and March 2023, over six million people died as a result of the respiratory disease COVID-19, and several hundred million were infected. The disease is caused by SARS-CoV-2, a coronavirus. “Coronaviruses are a group of RNA viruses that cause illnesses and diseases in mammals and birds”, explains European XFEL scientist Richard Bean. “However, despite their significant relevance for global human health, there is still a lot to learn about the structure and function of coronaviruses in general and SARS-CoV-2 in particular.”

In response to the outbreak of the pandemic, scientists and scientific organizations around the globe poured efforts into studying the structure, dynamics, and function of SARS-CoV-2 in search of vaccines and therapies. Due to its central role in the replication cycle of the virus, the main protease – an enzyme that liberates newly made pieces of the virus from one another – soon emerged as a key antiviral drug target. The main protease, or Mpro, is particularly attractive for drug development because it plays a central role in viral replication, and also because it is quite different from all human proteins. This allows therapies to specifically target the virus while minimizing side effects that might harm patients. Previous drug discovery programmes targeting other viruses have succeeded using viral protease inhibitors, making a successful outcome in the case of SARS-CoV-2 more likely. “While the height of the COVID-19 pandemic may have passed, there is still a lot of value in studying the SARS-CoV-2 virus”, enhances Thomas Lane from the Center for Free-Electron Laser Science (CFEL) in Hamburg. “COVID continues to present a significant health threat worldwide. Given the persistence of this virus and the possible emergence of future pathogenic coronaviruses, it is imperative we develop a deeper understanding of Mpro and its role in viral function.”

In a recent experiment at the SPB/SFX instrument at the European XFEL, Lane and colleagues used the intense X-ray beam to study Mpro. Several previous structural studies focusing on Mpro have highlighted a number of peculiarities. “Firstly, the protein forms a 3D structure known as a dimer when it is found in high concentrations”, explains European XFEL scientist Robin Schubert, who was involved in the experiment. “This structural habit seems to directly influence its activity—but we don’t know precisely why this is important for the virus.”

Read more on XFEL website

Image: An understanding of the structure and lifecycle of the SARS-CoV-2 virus is essential to develop vaccines and therapies.

Credit: CFEL

Unique Novel Drug Shows Promise Against SARS-CoV-2

Unique Novel Drug Shows Promise Against SARS-CoV-2

SARS-CoV-2 is an RNA virus that caused a three-year long pandemic with millions of reported deaths worldwide.1,2  Despite the unprecedented speed of development and approval of SARS-CoV-2 vaccines and oral antivirals especially Paxlovid (co-administered Nirmatrelvir with ritonavir), there remain risks for emerging variants of concern (VOCs) with increased virulence and infectivity, and clinical challenges especially for population at risk who cannot benefit from existing drugs due to potential drug-drug interactions (DDIs). Continued development of oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19.

Olgotrelvir (STI-1558) is designed as a potent standalone antiviral drug with excellent oral bioavailability, limited drug-drug interactions, and antiviral efficacy at doses with low safety concerns.  Olgotrelvir and its parent drug AC1115 potently inhibit activities of SARS-CoV-2 main protease (Mpro) including Mpro mutants found in SARS-CoV-2 VOCs, as well as Mpro mutants such as E166 found to be resistant to Paxlovid. In addition, olgotrelvir inhibits activity of human cathepsin L (CTSL), the major host cysteine protease aiding in virus entry through the endosomal pathway.3-5 The dual inhibition of both virus entry and virus replication pathways may enhance the robustness of the antiviral effect and reduce potential drug resistance. Indeed, olgotrelvir and AC1115 displayed potent antiviral activities against SARS-CoV-2 variants in cell-based models and in humanized transgenic mouse models. In phase 1 clinical trials, orally administered olgotrelvir demonstrated effective plasma exposure, limited mild adverse events, and a positive trend of reducing the SARS-CoV-2 viral RNA copy loads. Considering the favorable efficacy and pharmacokinetic profile along with data supporting the positive safety profile of the compound, olgotrelvir is a promising anti-SARS-CoV-2 drug candidate, which warrants further development as a next-generation therapeutic intervention for COVID-19 and potentially other coronaviruses.

Read more on SLAC website

Image: High resolution of co-crystal structure of SARS-CoV-2 Mpro or human cathepsin L complexed with AC1115. (A) SARS-CoV-2 Mpro (gray surface) bound with AC1115 (pink sticks). Electron density corresponding to AC1115 is shown in pink mesh. Hydrophobic residues of the Mpro catalytic active site binding pocket are labeled; with the active site cysteine shown in yellow. (B) Hydrogen bond interactions between AC1115 and Mpro are denoted with black lines. AC1115 forms 7 direct hydrogen bonds with Mpro residues, with additional polar interactions mediated by water molecules (red spheres). (C) CTSL protein (surface and cartoon) with covalently bound AC1115 (green sticks). Amino acid residues contacting AC1115 are labeled; the catalytic cysteine (Cys25) is additionally indicated by the yellow protein surface. (D) AC1115 hydrogen bonds with CTSL amino acids are shown (red dashed lines), along with the covalent bond to the Cys25 side chain sulfur atom (black line).   The two structures were deposited to PDB with IDs of 8UAB and 8UAC.

Researchers visualise in 3D how SARS-CoV-2 replicates in cells

Researchers visualise in 3D how SARS-CoV-2 replicates in cells

The use of different microscopy and tomography techniques, including synchrotron light, unveils how lung cells are modified along the infection in cell culture models. The work is the result of the European consortium CoCID (Compact Cell Imaging Device) with the participation of CSIC groups and the ALBA Synchrotron.

The covid-19 pandemic has affected more than 770 million people and has caused the death of nearly seven million people around the world. Its huge impact on health and global economy has promoted research in the field since 2020, although it is still necessary to understand how this infection makes progress with the aim of finding specific solutions to this pathogen. Now, a team from the Spanish National Research Council (CSIC) and the ALBA Synchrotron publishes in the journal ACS Nano the results obtained after three-dimensional analysis of the interior of an infected cell.

Members of the National Centre of Biotechnology (CNB-CSIC) and the ALBA Synchrotron, the only synchrotron light source in Spain located in Cerdanyola del Vallès (Barcelona), have imaged in three dimensions the interior of human lung epithelium cells, the primary target of the virus, and the severe structural changes caused by SARS-CoV-2 infection.

Pablo Gastaminza, CNB-CSIC researcher and main author of the work, explains the alterations they found: “when comparing an uninfected cell with an infected one, we can see that the virus multiplication machinery forms vesicles and tubules as well as remarkable signs of stress on cellular organelles such as mitochondria and the endoplasmic reticulum.”

The study is part of the collaboration established within the European CoCID (Compact Cell Imaging Device) consortium. It combines the use of molecular biology, virology and three types of microscopy techniques. One of them is the so-called soft X-ray cryo-tomography (Cryo-SXT), a technology available only in four places all over the world, including the MISTRAL beamline at the ALBA Synchrotron. This technique allows “to generate three-dimensional maps of the ultrastructure of complete cells, reconstructing their total volume and providing extra information to other techniques like electron microscopy,” according to Eva Pereiro, head of the MISTRAL beamline at ALBA.

Read more on ALBA website

Image: Three-dimensional images of a fragment of a control cell (left) and a cell infected with SARS-CoV-2 (right). The cell nucleus is highlighted in purple, healthy mitochondria in green, and mitochondria modified by the infection in red, the vacuoles in light blue, the viral factory in yellow and the viral particles in blue. 

Credit: ALBA Synchrotron/CNB-CSIC

Sirius helps reveal previously unknown process of maturation for key protein in SARS-CoV-2 replication

Sirius helps reveal previously unknown process of maturation for key protein in SARS-CoV-2 replication

Researchers at USP in São Carlos combined cutting-edge technologies and demonstrated that a molecule targeted by medications behaves differently than previously theorized.

A group of researchers from the University of São Paulo in São Carlos has just presented their findings from research indicating a new understanding of the maturation process and how inhibitors act upon the Mpro protein, an essential component in the life cycle of the Sars-CoV-2 virus and the target of various efforts to develop medications to treat Covid-19. Their results appear in an article entitled “An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition,” published in the journal Nature Communications (https://doi.org/10.1038/s41467-023-37035-5).

Mpro is an abbreviation for main protease, because of its importance to the virus. Today, two medications are available which interact with this molecule to treat covid-19. Still, some of the processes in this protein’s activity are not yet entirely understood, and this was the object of the study undertaken at Sirius.

As part of the role it plays in the life cycle of the Sars-CoV-2 virus, Mpro undergoes a series of modifications until it reaches its final form. Part of this process had already been described by the group from São Carlos, directed by Professor Glaucius Oliva.

André Godoy, who led the group, was one of the first external users of Sirius, the cutting- synchrotron light source planned and built by the Brazilian Center for Research in Energy and Materials (CNPEM), an organization overseen by the Ministry of Science, Technology and Innovation (MCTI).

In September 2020 he brought approximately 200 crystals containing proteins from the Sars-CoV-2 virus for analysis in the Manacá beamline, which was developed for experiments involving X-ray diffraction crystallography. “The Manacá beamline was the first research station to open at Sirius, as the result of a task-force effort at the CNPEM to support research exploring molecular mechanisms related to covid-19. This is one of the publications that resulted from this effort,” explains Harry Westfahl, Director of the Brazilian Synchrotron Light National Laboratory (LNLS).

Read more on the LNLS website

Image: Cryomicroscopy map of the Mpro dimer interacting with the N-terminal. Image obtained from analyses conducted at Diamond and Sirius by the USP São Carlos group

SARS-CoV-2 protein caught severing critical immunity pathway

SARS-CoV-2 protein caught severing critical immunity pathway

Powerful X-rays from SLAC’s synchrotron reveal that our immune system’s primary wiring seems to be no match for a brutal SARS-CoV-2 protein.

BY DAVID KRAUSE

Over the past two years, scientists have studied the SARS-CoV-2 virus in great detail, laying the foundation for developing COVID-19 vaccines and antiviral treatments. Now, for the first time, scientists at the Department of Energy’s SLAC National Accelerator Laboratory have seen one of the virus’s most critical interactions, which could help researchers develop more precise treatments.

The team caught the moment when a virus protein, called Mpro, cuts a protective protein, known as NEMO, in an infected person. Without NEMO, an immune system is slower to respond to increasing viral loads or new infections. Seeing how Mpro attacks NEMO at the molecular level could inspire new therapeutic approaches.

To see how Mpro cuts NEMO, researchers funneled powerful X-rays from SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) onto crystallized samples of the protein complex. The X-rays struck the protein samples, revealing what Mpro looks like when it dismantles NEMO’s primary function of helping our immune system communicate.

“We saw that the virus protein cuts through NEMO as easily as sharp scissors through thin paper,” said co-senior author Soichi Wakatsuki, professor at SLAC and Stanford. “Imagine the bad things that happen when good proteins in our bodies start getting cut into pieces.”

The images from SSRL show the exact location of NEMO’s cut and provide the first structure of SARS-CoV-2 Mpro bound to a human protein.

“If you can block the sites where Mpro binds to NEMO, you can stop this cut from happening over and over,” SSRL lead scientist and co-author Irimpan Mathews said. “Stopping Mpro could slow down how fast the virus takes over a body. Solving the crystal structure revealed Mpro’s binding sites and was one of the first steps to stopping the protein.”

The research team from SLAC, DOE’s Oak Ridge National Laboratory, and other institutions published their results today in Nature Communications.

Read more on the SLAC website

Synchrotron light proves effectiveness of several drugs in virus infections like SARS-CoV2

Synchrotron light proves effectiveness of several drugs in virus infections like SARS-CoV2

Microtubules are intracellular structures that function as true cellular highways for the transport of substances, vesicles, organelles and even viruses, in the case that a cell gets infected. In most viral infections, they are the transport routes to generate the viral factories, regions close to the nucleus where virus production is concentrated.

The idea is to design drugs that, by binding to microtubules, prevent viruses from using them during the infection process. In general, drugs that target microtubules are called MTAs (microtubule targeting agents). There are two types: stabilizers (MSA) and destabilizers (MDA). Both are widely available and most of these drugs are in the WHO Essential Medicines List, and hence, they are therapeutic alternatives that are affordable and available worldwide.

Researchers from CIB Margarita Salas selected 16 commercially available MTA (including 15 in clinical use) to analyse their capacity to inhibit the viral replication against 5 different virus: the human common cold coronavirus (HCoV), the pandemic SARS-CoV-2 coronavirus, the vesicular stomatitis virus, the poxvirus vaccinia and African swine fever virus.

Scientist confirmed that the MTA tested had an effect on virus replication and spreading and that this effect varies according to the virus dependency on the microtubular network. “The inhibitory effect obtained varied depending on the specific functions that viruses have developed throughout evolution to exploit cellular transport machinery”, explains Dra. Marian Oliva, researcher at CIB Margarita Salas-CSIC.

In particular, the most complex use of microtubules filaments might correspond to coronavirus (CoVs), such as the one responsible for the Covid-19 pandemic. Microtubules are necessary both for virus internalization and later at several levels of the formation of the viral replication site. In fact, S and M coronavirus proteins (located on the virus surface) interact with tubulin (protein that forms microtubules) during the infection, although their specific function is currently unknown. Various projects involving the use of the ALBA Synchrotron are under way to study deeper these aspects.

Read more on the ALBA website

Image: Image obtained at the XALOC beamline of ALBA. Drug mebendazole (MBZ) bounds to the protein that forms the microtubules: tubulin (T2RT and T1D).

Structural studies of SARS-CoV-2 nucleocapsid protein

Structural studies of SARS-CoV-2 nucleocapsid protein

Perspectives in relation to diagnosis and drug design

 A novel zoonotic coronavirus SARS-CoV-2 was originally explored in Wuhan, China in December 2019 and further regarded to the serious pandemic known as COVID-19. In early March 2022, the global COVID-19 pandemic has caused over 453 million confirmed cases and over 6 million deaths (John Hopkins Coronavirus Resource Center, https://coronavirus.jhu.edu).

 The COVID-19 virus and the emergence of new virus variants seriously threat to global public health. It is a strong requirement to develop the effective diagnostic tools which are able to quickly and reliably detect active SARS-CoV-2 infections.

 Structural proteins of the COVID-19 virus are very important to understand its pathogenic mechanism, thus leading to the development of antibodies, vaccines and drugs for targeting these proteins and viruses.

 SARS-CoV-2 comprised the four structural proteins; the spike (S), nucleocapsid (N), envelope (E) proteins and membrane glycoprotein (M). A complete virus particle (virion) is represented in Figure 1. Cryo-electron microscopy is one of the powerful tools to determine the overall structure of the S protein, thus presenting a unique crown or ‘corona’-like shape.

 Three viral proteins; the spike (S), envelope (E) and membrane (M) are embedded in the outer layer of the corona viral particle. The corona viruses protect themselves from the surrounding environment, then the ribonucleic acid (RNA) forms a stable packed in the lipid membrane. The nucleocapsid protein (nucleoprotein) is responsible for tightly wrap the RNA of viruses. However, the fatty membrane of SARS-CoV-2 is sensible to be destroyed by soap, detergent or surfactant.

 The nucleocapsid protein significantly involves in viral genomic RNA binding, thus protecting the coiled RNA as its genetic material inside the virus particle. Moreover, the N protein also plays an important role in the early stages of viral infection when the RNA genome is first released into the target host cell.

 X-ray crystal structures of the N-terminal (PDB entry 7CDZ) and C-terminal domains have been illustrated here (PDB entry 6WZO). Holo structure of N-terminal domain in complex with double strand RNA (PDB entry 7ACS) has been determined by Nuclear Magnetic Resonance Spectroscopy technique.

Read more on the Thai Synchrotron website

Image:  Three dimensional models of the SARS-CoV-2 virion and a schematic diagram of its four structural proteins. 

Credit: Figures were modified from coronavirusexplained     

Light sources have demonstrated huge adaptability during the pandemic

Light sources have demonstrated huge adaptability during the pandemic

Johanna Hakanpää is the beamline scientist for P11, one of the macromolecular crystallography beamlines at PETRAIII at DESY in Hamburg. Originally from Finland, she studied chemistry and then did her masters and PhD work in protein crystallography. Johanna was drawn to the field because she wanted to understand how life really works. Supporting health related research is important to her and Johanna is especially inspired by her son who is a patient of celiac disease. Together they hope that one day, with the help of science, he will be able to eat normally without having to think about what is contained in his food. Johanna started her light source journey as a user and was really impressed by the staff scientists who supported her during her experiments. This led her to apply for a beamline scientist position and she successfully made the transition, learning the technical aspects of the beamlines on the job.

In her #LightSourceSelfie, Johanna highlights the adaptability of light sources during the pandemic as a key strength. Being part of a team that was able to keep the lights on for users via remote experiments is a reflection of the commitment that Johanna and her colleagues have when it comes to facilitating science. Thousands of staff at light sources all around the world have shown the same commitment, ensuring scientific advances can continue. This is particularly true for vital research on the SARS-CoV-2 virus itself. Learn more about this research here: https://lightsources.org/lightsource-research-and-sars-cov-2/

Crossing the border for understanding how life is assembled

Crossing the border for understanding how life is assembled

Ana’s #LightSourceSelfie from the ALBA synchrotron in Spain

Ana Joaquina Pérez-Berná is a beamline scientist at the ALBA synchrotron near Barcelona in Spain.

As a biologist working on the soft X-ray cryo tomography beamline (MISTRAL), her role involves supporting the users with their experiments and also doing her own research. The beamline’s capabilities enable scientists to study down at the cellular level and the research covers a wide variety of diseases such as malaria, zika virus and SARS-CoV-2, along with treatments such as antivirals and chemotherapy. When describing her work, Ana says, “You are the first person who can enter the cell and see how it is inside, discover how the virus builds its bio-factories inside the cells, or discover how therapies work. Crossing that border for understanding how life is assembled, that is a privilege!”

Lightsource research on SARS-CoV-2

Lightsource research on SARS-CoV-2

Coronaviruses are a family which includes the common cold, SARS, MERS and the current outbreak of the disease COVID-19, caused by the SARS-CoV-2 virus.
Several facilities of our collaboration have started research about SARS-CoV-2 virus or launched open calls for rapid access. This post will be updated regularly.

Publications on SARS-CoV-2 Rapid Access




Publications

Published articles

2021.12.09 Diamond Light Source (UK) article on their website: Trigger of rare blood clots with AstraZeneca and other COVID vaccines found by scientists

2021.11.06 APS at Argonne National Laboratory (USA) article on their website: Advanced Photon Source Helps Pfizer Create COVID-19 Antiviral Treatment

2021.11.04 ESRF (France) article on their website: EBS X-rays show lung vessels altered by COVID-19 (esrf.fr)

2021.08.11 BESSY II at HZB (Germany) article on their website: HZB coordinates European collaboration to develop active agents against Corona – Helmholtz-Zentrum Berlin (HZB) (helmholtz-berlin.de)

2021.08.10 Canadian Light Source article on their website: Developing antiviral drugs to treat COVID-19 infections

2021.07.06 European XFEL (Germany) article on their website: XFEL: Insights into coronavirus proteins using small angle X-ray scattering

2021.06.21 Diamond Light Source (UK) article on their website: X-ray fluorescence imaging at Diamond helps find a way to improve accuracy of Lateral Flow Tests

2021.06.17 Australian Synchrotron (ANSTO) article on their website: Research finds possible key to long term COVID-19 symptoms

2021.05.11 Swiss Light Source at PSI (Switzerland) article on their website: How remdesivir works against the coronavirus

2021.05.28 SLAC (CA / USA) article from the Stanford Synchrotron Radiation Lightsource (SSRL): Structure-guided Nanobodies Block SARS-CoV-2 Infection | Stanford Synchrotron Radiation Lightsource

2021.05.21 ALS (USA) article on their website: Guiding Target Selection for COVID-19 Antibody Therapeutics

2021.05.21 ESRF (France) article on their website: Combatting COVID-19 with crystallography and cryo-EM (esrf.fr)

2021.05.18 ALS (USA) article on their website: How X-Rays Could Make Reliable, Rapid COVID-19 Tests a Reality | Berkeley Lab (lbl.gov)

2021.04.27 Canadian Light Source (Canada), video on their website Investigating the long-term health impacts of COVID-19 (lightsource.ca)

2021.04.22 Synchrotron Light Research Institute (Thailand), article on their website: SLRI Presented Innovations Against COVID-19 Outbreak to MHESI Minister on His Visit to a Field Hospital at SUT

2021.04.16 Diamond Light Source (UK) article on their website: Massive fragment screen points way to new SARS-CoV-2 inhibitors

2021.04.14 SLAC (CA / USA), article also with news about research at Stanford Synchrotron Radiation Lightsource (SSRL):Researchers search for clues to COVID-19 treatment with help from synchrotron X-rays

2021.04.07 Diamond Light Source (UK), article on their website: First images of cells exposed to COVID-19 vaccine – – Diamond Light Source

2021.04.05 ALS (CA/USA) blog post on Berkeley Lab Biosciences website: New COVID-19 Antibody Supersite Discovered

2021.04.02 PETRA III at DESY (Germany), article and animation on their website DESY X-ray lightsource identifies promising candidate for COVID drugs

2021.03.26 Diamond Light Source (UK), article on their website: New targets for antibodies in the fight against SARS-CoV-2

2021.02.23 Australian Light Source (ANSTO) Australia, article on their website: Progress on understanding what makes COVID-19 more infectious than SARS

2020.12.02 ESRF (France), article and video on their website: ESRF and UCL scientists awarded Chan Zuckerberg Initiative grant for human organ imaging project

2020.11.10 Diamond Light Source (UK), article and video on their website: From nought to sixty in six months… the unmasking of the virus behind COVID-19

2020.10.29 Canadian Light Source (Canada) video on their website: Studying how to damage the COVID-19 virus

2020.10.07 National Synchrotron Light Source II (NSLS-II) at Brookhaven Lab (NY / USA) article on their website: Steady Progress in the Battle Against COVID-19

2020.10.07 Diamond Light Source (UK), article on their website: Structural Biology identifies new information to accelerate structure-based drug design against COVID-19

2020.10.06 MAX IV (Sweden), article on their website: Tackling SARS CoV-2 viral genome replication machinery using X-rays

2020.08.31 SLAC (CA / USA), article also with news about research at Stanford Synchrotron Radiation Lightsource (SSRL): SARS-CoV-2 Spike Protein Targeted for Vaccine

2020.08.27 Diamond Light Source (UK), article on their website: Structural Biology reveals new target to neutralise COVID-19

2020.08.27 Canadian Light Source (Canada) video on their website: Developing more effective drugs

2020.08.25 Australian Synchrotron (ANSTO) (Australia) article on their website: More progress on understanding COVID-19

2020.08.24 DESY (Germany) article on their website: PETRA III provides new insights into COVID-19 lung tissue

2020.08.11 Australian Synchrotron (ANSTO) (Australia) article on their website: Unique immune system of the alpaca being used in COVID-19 research

2020.07.30 Swiss Light Source at PSI (Switzerland) article on their website: COVID-19 research: Anti-viral strategy with double effect

2020.07.29 National Synchrotron Light Source II (NSLS-II) at Brookhaven Lab (NY / USA) article on their website: Ready to join the fight against COVID-19.

2020.07.20 ALBA (Spain) article on their website: A research team from Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC) uses synchrotron light to study the possible effect of an antitumoral drug of clinical use over the viral cycle of SARS-CoV-2 coronavirus. 

2020.07.15 ALS (USA) article on their website: Antibody from SARS Survivor Neutralizes SARS-CoV-2

2020.07.14 Diamond Light Source (UK), article on their website: Engineered llama antibodies neutralise Covid-19 virus

2020.06.17 European XFEL (Germany) article on their website: Pulling Together: A collaborative research approach to study COVID-19

2020.06.15 European XFEL (Germany) article on their website: Open Science COVID19 analysis platform online

2020.06.09 APS at Argonne National Laboratory (USA) article on their website: Novel Coronavirus Research at the Advanced Photon Source

2020.05. Società Italiana di Fisica publishes an article about research done at Elettra Sincrotrone Trieste (Italy) and the Advanced Light Source (CA / USA): Accelerator facilities support COVID-19-related research

2020.05.27 Diamond Light Source (UK), new animation video demonstrating the work that has been done at Diamond’s XChem facilities.

2020.05.19 Advanced Light Source (CA / USA), article about their latest results: X-ray Experiments Zero in on COVID-19 Antibodies

2020.05.15 Swiss Light Source (Switzerland), article about their first MX results: First MX results of the priority COVID-19 call

2020.05.14 MAX VI (Sweden), article about their research: Tackling SARS CoV-2 viral genome replication machinery using X-rays

2020.05.14 CHESS (NY/USA), article: CHESS to restart in June for COVID-19 research

2020.05.14 the LEAPS initiative brings together many of our European members. The initative published this brochure: Research at LEAPS facilities fighting COVID-19

2020.05.12 Diamond Light Source (UK), article about their collaboration in a consortium: UK consortium launches COVID-19 Protein Portal to provide essential reagents for SARS-CoV-2 research

2020.05.11 Advanced Photon Source (IL/USA), article: Studying Elements from the SARS-CoV-2 Virus at the Bio-CAT Beamline

2020.05.07 European XFEL (Germany), article: European XFEL open for COVID-19 related research

2020.05.06 ESRF (France), article: World X-ray science facilities are contributing to overcoming COVID-19

2020.04.29. BESSY II at HZB (Germany), article: Corona research: Consortium of Berlin research and industry seeks active ingredients

2020.04.29. Swiss Light Source and SwissFEL at PSI (Switzerland), interview series on the PSI website: Research on Covid-19

2020.04.23. PETRA III at DESY (Germany), article: X-ray screening identifies potential candidates for corona drugs

2020.04.21. MAX IV (Sweden), article: BioMAX switches to remote operations in times of COVID-19

2020.04.16. SLAC (CA / USA), article also with news about research at Stanford Synchrotron Radiation Lightsource (SSRL): SLAC joins the global fight against COVID-19

2020.04.15 Berkeley National Lab (CA/ USA), article with a focus on the research at the Advanced Light Source (ALS):
Staff at Berkeley Lab’s X-Ray Facility Mobilize to Support COVID-19-Related Research

2020.04.07 Diamond Light Source (UK), article: Call for Chemists to contribute to the fight against COVID-19
Crowdfunding: COVID-19 Moonshot

2020.04.07. ANSTO’s Australian Synchrotron (Victoria), article: Aiding the global research effort on COVID-19

2020.04.06. National Synchrotron Light Source II (NSLS-II) at Brookhaven Lab (NY / USA), article: Brookhaven Lab Mobilizes Resources in Fight Against COVID-19

2020.04.02. BESSY II at HZB (Germany), article: Corona research: Two days of measuring operation to find the right key

2020.03.31 Diamond Light Source (UK), article: Jointly with Exscientia and Scripps Research, Diamond aims to accelerate the search for drugs to treat COVID-19

2020.03.27 Argonne National Laboratory with the Advanced Photon Source (APS) and other facilities on-site (IL / USA), article: Argonne’s researchers and facilities playing a key role in the fight against COVID-19

2020.03.27 ANSTO’s Australian Synchrotron (Victoria), article and video: Helping in the fight against COVID-19

2020.03.25 PETRA III at DESY (Germany), article: Research team will X-ray coronavirus proteins

2020.03.23 Diamond Light Source (UK) releases its first animation explaining: SARS-CoV-2 Mpro Single Crystal Crystallography

2020.03.25 CERN Courrier (Switzerland) article about synchrotron research on SARS-CoV-2, written by Tessa Charles (accelerator physicist at the University of Melbourne currently based at CERN, completed her PhD at the Australian Synchrotron): Synchrotrons on the coronavirus frontline

2020.03.19 BESSY II at Helmholtz-Zentrum Berlin (Germany), research publication: Coronavirus SARS-CoV2: BESSY II data accelerate drug development

2020.03.19 BESSY II at Helmholtz-Zentrum Berlin (Germany), technique explanation webpage: Protein crystallography at BESSY II: A mighty tool for the search of anti-viral agents

2020.03.16 Diamond Light Source (UK), article on their “Coronavirus Science” website: Main protease structure and XChem fragment screen

2020.03.12. Elettra Sincrotrone (Italy), article on their website: New project to fight the spread of Coronavirus has been approved

2020.03.05. Advanced Photon Source (IL / USA), article on their website: APS Coronavirus Research in the Media Spotlight

2020.03.05. Advanced Photon Source (IL / USA), research publication: “Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2,” bioRXiv preprint  DOI: 10.1101/2020.03.02.968388, Article on their website (source: Northwestern University): New Coronavirus Protein Reveals Drug Target

Facility Covid-19 research pages

The Canadian Light Source (Canada) has created a specific page highlighting their COVID-19 research: COVID-19 research at the Canadian Light Source

BESSY II at HZB (Germany) has set up a page where it shows their contributions to the research on SARS-CoV-2 , see here

DESY (Germany) has launched a new page dedicated to Corona Research: https://www.desy.de/news/corona_research/index_eng.html

Diamond Light Source (UK) has created a specific website “Coronavirus Science” with platforms for various audiences: scientific community, general public and the media: https://www.diamond.ac.uk/covid-19.html

ELETTRA (Italy) has launched a new page dedicated to COVID-19 research: https://www.elettra.eu/science/covid-19-research-at-elettra.html

The Photon Division of PSI (Switzerland) have collated many information linked to their institute on coronavirus-relevant research (recent publications, rapid access…): https://www.psi.ch/en/psd/covid-19

ALBA (Spain) has set up a dedicated area on their website for information related to COVID-19 (rapid access, publications etc): https://www.albasynchrotron.es/en/covid-19-information/

The ALS (CA/USA) has created a page listing all COVID-19 related research: https://als.lbl.gov/tag/covid-19/




Rapid access

Scientists can apply for rapid access at following facilities (only member facilities of Lightsources.org are referenced, the most recent published (or updated) call is mentioned first).

  • The National Synchrotron Light Source II (NSLS-II) in NY / USA is offering a streamlined and expedited rapid access proposal process for groups that require beam time for structural biology projects directly related to COVID-19. The Center for Biomolecular Structure team is supporting remote macromolecular crystallography experiments at Beamlines 17-ID-1 (AMX) and 17-ID-2 (FMX) in this research area. To submit a macromolecular crystallography proposal for COVID-19 related research, use the following form:
    https://surveys.external.bnl.gov/n/RapidAccessProposal.aspx
  • The Advanced Photon Source (APS) at Argonne National Laboratory in IL / USA  user program is operational to support:

·         Research on SARS-CoV-2 or other COVID-19-related research that addresses the current pandemic.

·         Critical, proprietary pharmaceutical research.

·         Mail-in/remote access work for any research involving low-risk samples and most medium-risk samples (as defined on the APS ESAF form).

·         Limited in situ research (set-up with one person, and ability to carry out majority of experiment safely remotely)
https://www.aps.anl.gov/Users-Information/About-Proposals/Apply-for-Time

PETRA III at DESY in Germany offers also Fast Track Access for Corona-related research:
https://photon-science.desy.de/users_area/fast_track_access_for_covid_19/index_eng.html

Australian Synchrotron at ANSTO makes its macromolecular crystallography beamlines available to structural biologists in response to the COVID-19 pandemic: https://www.ansto.gov.au/user-access

North American DOE lightsource facilities have created a platform to enable COVID-19 research. There you can find ressources and points of contact to request priority access:
Structural Biology Resources at DOE Light Sources

Elettra Sincrotrone Trieste in Italy opens to remote acces following beamlines: XRD1, XRD2, SISSI-BIO and MCX thanks to an CERIC-ERIC initiative:
https://www.ceric-eric.eu/2020/03/10/covid-19-fast-track-access/
http://www.elettra.eu/userarea/user-area.html

The Advanced Light Source (ALS) at LBNL in California / USA has capabilities relevant to COVID-19 and researchers can apply through their RAPIDD mechanism:
https://als.lbl.gov/apply-for-beamtime/

ALBA Synchrotron in Spain offers a COVID-19 RAPID ACCESS on all beamlines:
https://www.albasynchrotron.es/en/en/users/call-information

SOLARIS Synchrotron in Poland gives acces to its Cryo Electron Microscope thanks to an CERIC-ERIC initiative: https://www.ceric-eric.eu/2020/03/10/covid-19-fast-track-access/

Swiss Light Source and Swiss FEL at PSI in Switzerland offer priority access to combating COVID-19:
https://www.psi.ch/en/sls/scientific-highlights/priority-access-call-for-work-on-combating-covid-19

Diamond Light Source in the United Kingdom opened also a call for rapid access:
https://www.diamond.ac.uk/Users.html

Image: Electron density at the active site of the SARS-CoV-2 protease, revealing a fragment bound
Credit: Diamond Light Source

APS helps Pfizer create Covid-19 antiviral treatment

APS helps Pfizer create Covid-19 antiviral treatment

Pharmaceutical company Pfizer has announced the results of clinical trials of its new oral antiviral treatment against COVID-19. The new drug candidate, Paxlovid, proved to be effective against the SARS-CoV-2 virus, which causes COVID-19, according to results released by Pfizer on Nov. 5.

Scientists at Pfizer created Paxlovid with the help of the ultrabright X-rays of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory.

“Today’s news is a real game-changer in the global efforts to halt the devastation of this pandemic,” said Albert Bourla, chairman and chief executive officer of Pfizer, in a company press release. ​“These data suggest that our oral antiviral candidate, if approved or authorized by regulatory authorities, has the potential to save patients’ lives, reduce the severity of COVID-19 infections and eliminate up to nine out of 10 hospitalizations.”

DOE invests in user facilities such as the APS for the benefit of the nation’s scientific community, and supports biological research as part of its energy mission. This research has been critical in the fight against COVID-19. The DOE national laboratories formed the National Virtual Biotechnology Laboratory (NVBL) consortium in 2020 to combat COVID-19 using capabilities developed for their DOE mission, and that consortium helps support research into antiviral treatments such as Paxlovid.

Work to determine the structure of the antiviral candidate was done at the Industrial Macromolecular Crystallography Association Collaborative Access Team (IMCA-CAT) beamline at the APS, operated by the Hauptman-Woodward Medical Research Institute (HWI) on behalf of a collaboration of pharmaceutical companies, of which Pfizer is a member.

As a member of IMCA-CAT, Pfizer routinely conducts drug development experiments at the APS, and the process of narrowing down and zeroing in on this drug candidate was performed over many months, according to Lisa Keefe, executive director of IMCA-CAT and vice president for advancing therapeutics and principal scientist at Hauptman-Woodward Medical Research Institute. IMCA-CAT, she said, delivers quality results in a timely manner, much faster than the home laboratories of the companies themselves can do.

Read more on the APS website

Image: The IMCA-CAT beamline at the Advanced Photon Source, where work was done to determine the structure of Pfizer’s new COVID-19 antiviral treatment candidate.

Credit: Lisa Keefe, IMCA-CAT/Hauptman-Woodward Medical Research Institute

Nanobodies against SARS-CoV-2

Nanobodies against SARS-CoV-2

Göttingen researchers have developed nanobodies – a type of antibodies – that efficiently block the coronavirus SARS-CoV-2 and its new variants. Those nanobodies, which originate from alpacas inoculated with part of the SARS-CoV-2 virus spike protein – the receptor-binding domain that the virus deploys for invading host cells – could serve as a potent drug against COVID-19. The researchers used the X10SA crystallography beamline at the Swiss Light Source to characterize the interaction between the nanobodies and the coronavirus spikes at the molecular level.


Unlike antibodies, nanobodies can be produced on an industrial scale and at a low cost and therefore meet the global demand for COVID-19 therapeutics. The new nanobodies, which can bind and neutralize the virus up to 1000 times better than previously developed antibodies, are currently in preparation for clinical trials.

Read more on the PSI website

Image: The figure shows how two of the newly developed nanobodies (blue and magenta) bind to the receptor-binding domain (green) of the coronavirus spike protein (grey), thus preventing infection with SARS-CoV-2 and its variants.

Credit: Thomas Güttler / Max Planck Institute for Biophysical Chemistry

Developing antiviral drugs to treat COVID-19 infections

Developing antiviral drugs to treat COVID-19 infections

The rapid development of safe and effective vaccines has helped bring the pandemic under control. However, with the rise of variants and an uneven global distribution of vaccines, COVID-19 is a disease we will have to manage for some time.

Antiviral drugs that target the way the virus replicates may be the best option for treating outbreaks of COVID-19 in unvaccinated and under-vaccinated populations.

Using the Canadian Light Source (CLS) at the University of Saskatchewan, researchers from the University of Alberta (U of A) have isolated some promising inhibitors that could be used to treat COVID-19 infections. The scientists used the synchrotron remotely during the facility’s special COVID-19 call for proposals, an initiative created to support research to help fight the pandemic.

The team’s findings have been recently published in the European Journal of Medicinal Chemistry.

“With the help of the CLS, and the multiple teams here at the U of A, including the our lab and the Young lab in the Department of Biochemistry, Vederas lab in the Department of Chemistry, and Tyrrell team in Medical Microbiology and Immunology Department, we’ve been very efficient at developing a group of inhibitors that is very promising,” said Joanne Lemieux, a professor at the U of A.

Read more on the CLS website

Image: Michel Fodje, CLS Senior Scientist, using the CMCF beamline at the CLS, which was used for this project.

Credit: Canadian Light Source