Tag: virus

Access denied: Stopping rabies virus from entering cells

Access denied: Stopping rabies virus from entering cells

Structural insights pave the way for development of new vaccines and therapies against rabies

Rabies virus can cause fatal neurological disease when access to medication is scarce. Tackling this issue will require novel vaccines and therapies to be developed and the viral surface protein may be a suitable target for these interventions. This protein arranges in triplets, but the structure of this arrangement has not yet been determined and the interaction between this triplet and therapeutic agents remains to be characterised. In a recent publication in Cell Host & Microbe, a research team at the University of Oxford collaborated with the electron Bio-Imaging Centre (eBIC) at Diamond Light Source to solve the cryo-electron microscopy (cryo-EM) structure of the triplet in complex with two therapeutic agents. Building on this work, the scientists investigated the mechanism by which licensed therapies inhibit the viral protein. The structural insight gained from this work will allow for strategic development of new vaccines and therapies against the virus.

A growing medical concern with limited treatments

Rabid animals typically spread rabies virus to humans by biting and this can cause a lethal neurological infection. Despite the development of vaccines and therapeutics, over 60,000 people die each year from rabies. Most of these deaths occur in African and Southeast Asian countries, where the virus is endemic in animals and access to medical intervention is insufficient. There is a growing necessity to design accessible therapeutics in response. Currently, vaccines can prevent rabies, but multiple doses are often required to achieve protection. Exposed individuals can additionally be treated with antibodies — components of the immune system that detect and block specific microorganisms (e.g. bacteria or viruses). There is concern however that currently available antibodies may not be protective against new variants of the virus and additional antibodies need to be produced.

A dynamic viral protein drives virus entry into the cell

Vaccines and antibody therapies target a single protein on the surface of the rabies virus. This aptly named ‘fusion’ protein engages with cellular proteins and triggers fusion of the virus with the cell, allowing infection to begin. Fusion proteins come together in triplets and change shape to drive fusion. The triplets initially form an open tripod (i.e. in which the three ‘legs’ are splayed). To allow fusion, the legs then fold into a closed-tripod arrangement. The researchers purified the fusion protein as a triplet in the open-tripod arrangement to study its architecture and association with antibodies.

Read more on the Diamond website

Image: Graphical abstract from DOI: 10.1016/j.chom.2022.07.014

Credit: reused under the CC BY 2.0 license

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

Virus recognition skills

Virus recognition skills

A virus recognizes the starting point on the DNA to be packaged inside its protein shell

A bacteriophage – a virus that attacks bacteria – assembles into an infectious species using a powerful nanomachine to stuff its DNA into a protein shell. In several types of phage, this genome packaging motor is composed of several copies of large and small terminase subunits (TerL and TerS, respectively) that attach to a portal into the protein procapsid. 

Figure 1. Envelope of NV1 TerS from SAXS data, overlaid with modeled structure with open HTHs. Circle highlights one HTH motif.

The Cingolani group (Thomas Jefferson U) has now determined the structure of TerS from the Pseudomonas phage PaP3. Phage DNA to be packaged contains multiple copies of the genome, but just one copy is needed to fill a procapsid. Terminases attempt to package this one copy by various methods; in PaP3 a termination signal is provided by the interaction of a specific sequence in the DNA (the cos sequence) with TerS.

A crystal structure of PaP3 TerS reveals a nonameric ring of mixed alpha/beta composition, sitting atop a 9-stranded beta-barrel. Projecting out from the ring are spokes tipped with helix-turn-helix (HTH) DNA-binding domains. In the crystal, with no DNA present, the HTH domains are packed tightly against the inner parts of the nonamer (a “closed” form). Crystals of TerS from the related NV1 phage were also studied; their quality was not as good but the same conformation was found.  BioSAXS coupled to size-exclusion chromatography, at CHESS, was then used to examine the PaP3 TerS structure, and that of the related NV1 protein, in solution. Both turned out to be ~25% larger than predicted from the crystal structure. The molecular envelope determined from SAXS data for NV1 clearly showed protuberances on the outside of the nonameric ring that did not match the crystal structure. However, by rotating the HTH domain of each monomer about an obvious hinge region, an “open” model could be built that fit the SAXS envelope well (Figure 1). 

Read more on the CHESS website

Image: Figure 1. Envelope of NV1 TerS from SAXS data, overlaid with modeled structure with open HTHs. Circle highlights one HTH motif.

Expansion of SOLARIS experimental hall

Expansion of SOLARIS experimental hall

The SOLARIS Centre has been awarded by the Ministry of Science and Higher Education a grant for the expansion of the experimental hall. This long-awaited decision opens up new perspectives for the development of the Centre.

The area of ​​the synchrotron hall will be increased by over two thousand square meters. This space will enable the construction of four new beamlines, which require a long distance of the sample from the synchrotron radiation source. These new facilities include the SOLCRYS beamline for the structural research. The beamline end stations will enable analyses of the structure of proteins, viruses, nucleic acids, and polymers. These studies provide knowledge on the molecular structure of the basic building blocks of living organisms, including the architecture of macromolecules. Research carried out on the beamline will be used, among others, in biological sciences, medicine (drug design and discovery), chemistry, and materials science. SOLCRYS will be the only research infrastructure of this type not only in Poland, but also in the entire Central and Eastern Europe.

Read more on the SOLARIS website

Image: Visualisation of the new building.

Pirbright Institute grants a new licence for FMDV vaccine development

Pirbright Institute grants a new licence for FMDV vaccine development

The Pirbright Institute and its research partners have granted MSD Animal Health an exclusive commercial licence for a new, effective and affordable vaccine to protect livestock against several serotypes of foot-and-mouth disease virus (FMDV). The new vaccine is more stable than current foot-and-mouth disease (FMD) vaccines and is less reliant on a cold-chain during vaccine distribution – characteristics that give the vaccine greater potential for helping to relieve the burden placed on regions where the disease is endemic in large parts of Africa, the Middle East and Asia. These developments have been possible, thanks to a long-standing collaboration between Diamond Light Source, Pirbright, the University of Oxford, the University of Reading and MSD Animal Health, and the vaccine has been developed over the years from basic science to animal trials. This work has been supported by funding from the Wellcome Trust to speed up commercialisation.

Professor David Stuart, Life Sciences Director at Diamond Light Source and MRC Professor in Structural Biology at the University of Oxford, noted:

We have been working to achieve something close to the holy grail of vaccines. Instead of traditional methods of vaccine development, using infectious virus as its basis, our team synthetically created empty protein shells to imitate the protein coat that forms the strong outer layer of the virus. Diamond’s visualisation capabilities and the expertise of Oxford University in structural analysis and computer simulation, enabled us to visualise in detail something invisible in a normal microscope and to enhance the design, atom by atom, of the empty shells. The key thing is that unlike the traditional FMDV vaccines, there is no chance that the empty shell vaccine could revert to an infectious form. The licence that has just been granted suggests that the work will have a broad and enduring impact on vaccine development.

>Read more on the Diamond Light Source website

Understanding the viruses that kill cancer cells

Understanding the viruses that kill cancer cells

Taking inspiration from virology to find better treatments for cancer

There are some viruses, called oncolytic viruses, that can be trained to target and kill cancer cells. Scientists in the field of oncolytics want to engineer these viruses to make them safer and more effective so they can be used to treat more people and different types of cancers. To achieve this, they first have to fully understand at the molecular level all the different ways that the virus has evolved to infect healthy cells and cause disease. A research team from Cardiff University set out to better understand how a protein on the surface of a virus often used to kill cancer, called an adenovirus, binds to human cells to cause an infection. Using X-ray crystallography, the team was able to determine the structure of one the key adenovirus proteins. Using this information and after extensive computational analysis, the research team realised the virus was not binding the receptor on the cells that was originally thought. This has important implications for the development of new virotherapies and engineering of viruses to treat cancer. The more thoroughly the researchers can understand how the adenoviruses interact with cancer cells at the molecular level, the more safe and effective treatments can be brought to clinical trial in the future.

>Read more on the Diamond Light Source website

New possibilities against the HIV epidemic

New possibilities against the HIV epidemic

Research identifies new antibodies with potent activity against virus and infected cells

The Human Immunodeficiency Virus type-1 (HIV-1) currently infects 37 million people worldwide, with an additional 2 million new infections each year. Following infection, the virus has a long period of latency, during which it multiplies without causing symptoms. HIV attacks the cells of the immune system, especially the cells called CD4+ T-lymphocytes, which are responsible for triggering the body’s response chain against infections. Thus, by suppressing the action of the immune system, the virus destroys the body’s ability to defend itself against other diseases, leading to the so-called Acquired Immunodeficiency Syndrome, or AIDS.
Even with the development of antiretroviral therapies that have improved quality of life and increased the life expectancy of patients with HIV/AIDS, it is widely accepted that the only way to effectively curb this devastating epidemic is through the development of an HIV-1 vaccine.

>Read more on the Brazilian Synchrotron Light Laboratory website

Image: Part of the structure of the CAP228-16H protein with the region of the V2 loop highlighted in yellow. (Full image here)

Secrets of the deadly white-tail virus revealed

Secrets of the deadly white-tail virus revealed

The inner workings of a lethal giant freshwater prawn virus have been revealed by an international team of researchers using data gathered at Diamond Light Source. The results reveal a possible new class of virus and presents the prospect of tackling a disease that can devastate prawn farms around the world.

The detailed structure of a virus that can devastate valuable freshwater prawn fisheries has been revealed by an international team using image data collected in the Electron Bio-Imaging Centre (eBIC) based at Diamond Light Source. The researchers produced high-resolution images of virus like particles, VLP’s, composed of virus shell proteins which they compared with lower resolution images of the complete virus purified from prawn larvae. They found strong similarities between the two suggesting that the more detailed VLP images are a good representation of the intact virus. This research, exposing the inner workings of the MrNV, could make it easier to develop ways of combating the economically important disease, but also suggests that it belongs in a new, separate, group of nodaviruses.
The researchers used the rapidly developing technique of cryo-electron microscopy, cryoEM, which has the ability to produce very high-resolution images of frozen virus particles. Images so detailed that the positions of individual atoms could be inferred. Recent breakthroughs in this technique have transformed the study of relatively large biological complexes like viruses allowing researchers to determine their structures comparatively quickly. The data to produce the MrNV structure described here was captured in two days at the eBIC facility.

>Read more on the Diamond Light Source website

Image: 3D model of the MrNV
Credit: Dr David Bhella

Insights into an antibody directed against dengue virus

Insights into an antibody directed against dengue virus

We are one step further to uncovering a new way to stave off dengue fever thanks to important work carried out at the I02 beamline at Diamond Light Source.

The study, recently published in Nature Immunology, describes how an antibody effectively targets the dengue virus.
Dengue virus affects hundreds of millions of people worldwide and is an untreatable infection. Secondary infections with dengue can lead to a life-threatening form of the disease due to a phenomenon called antibody-dependent enhancement (ADE). Additionally, efforts to develop a vaccine against the virus have been hindered by ADE.

A huge collaborative effort sought to investigate ADE in dengue, and two antibodies were characterised that bound to the envelope protein of the dengue virus. One of the antibodies was found to be a potent neutraliser of the virus, but importantly was unable to promote ADE.

>Read more on the Diamond Light Source website

Image: Fab binding in the context of the mature virion. e, Comparison of 2C8 Fab and 3H5 Fab docked onto a E dimer. 2C8 (green) and 3H5 (orange) Fabs were docked onto PDB ID 3J27 by aligning the EDIII potion of the structures. The Fabs are shown as surfaces and the E dimer is displayed in cartoon representation. A side view is of the E dimer on the viral surface is shown. The approximate location of the viral membrane is shown schematically.

 

Snaphot of molecular mechanism at work in lethal virus

Snaphot of molecular mechanism at work in lethal virus

X-ray crystallography at the Australian Synchrotron contributed to major research findings.

Data collected on the macromolecular crystallography beamlines at the Australian Synchrotron has contributed to major research findings on two deadly viruses, Hendra and Nipah, found in Australia, Asia and Africa. The viruses can be transmitted to humans not directly by the bat which is the natural carrier but by an infected animal like horses or pigs.

Beamline scientist, Dr David Aragao (pictured above), a co-author on the paper in Nature Communications, said that obtaining a clear motion picture of key biological process at the molecular level of viruses is often not available with current biomedical techniques.
“However, using X-ray crystallography from data collected on both MX1 and MX2 beamlines at the Australian Synchrotron, we were able to obtain  8  ‘photograph-like’ snapshots of the molecular process that allows the Hendra and Nipah virus to replicate.“

Two authors of the paper, PhD students Kate Smith and Sofiya Tsimbalyuk, who are co-supervised by Aragao and his collaborator Professor of Biochemistry Jade Forwood of the Graham Centre for Agricultural Innovation Charles Sturt University, used the Synchrotron extensively collecting multiple data sets that required extensive refinements over two years to isolate the mechanism of interest.

>Read more on the Australian Synchrotron website

Image: Beamline scientist, Dr David Aragao.

Respiratory virus study points to likely vaccine target

Respiratory virus study points to likely vaccine target

The work provides a promising route for designing a vaccine effective against a broad range of RSV strains, which cause serious respiratory disease in infants and older adults.

Respiratory syncytial virus (RSV) causes 118,000 deaths in young children each year worldwide and 57,000 hospitalizations of children each year in the United States alone. Attempts to develop a vaccine—at first based on inoculations with inactivated virus, and then targeting a key viral surface protein (RSV F)—have failed. Recent studies, however, suggest that a second viral surface protein (RSV G) is a promising target.

In one earlier study, elevated concentrations of antibodies targeting both RSV F and RSV G were associated with lower clinical disease severity scores, despite a substantially lower absolute abundance of anti-G antibodies. Another study found that higher levels of maternal anti-G antibodies correlated with less severe disease in infants (up to 4-6 months of age), even though anti-G antibodies were again found in lower concentrations.

While the RSV F surface protein allows the virus to enter a host cell, RSV G is what allows the virus to stick to lung cells and distort immune responses. This disruption of the immune response by RSV G might explain why vaccines based on RSV F have failed. Thus, a protective antibody response that blocks RSV G activity could be more effective, but scientists didn’t know how antibodies target RSV G at the molecular level.

>Read more on the ALS website.

Image: Stanislav Fedechkin and Rebecca DuBois.
Credit: C. Lagattuta/UC Santa Cruz

Scientists develop sugar-coated nanosheets to target pathogens

Scientists develop sugar-coated nanosheets to target pathogens

Molecular Foundry-designed 2-D sheets mimic the surface of cells

Researchers have developed a process for creating ultrathin, self-assembling sheets of synthetic materials that can function like designer flypaper in selectively binding with viruses, bacteria, and other pathogens.
In this way the new platform, developed by a team led by scientists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), could potentially be used to inactivate or detect pathogens.

The team, which also included researchers from New York University, created the synthesized nanosheets at Berkeley Lab’s Molecular Foundry, a nanoscale science center, out of self-assembling, bio-inspired polymers known as peptoids. The study was published earlier this month in the journal ACS Nano.
The sheets were designed to present simple sugars in a patterned way along their surfaces, and these sugars, in turn, were demonstrated to selectively bind with several proteins, including one associated with the Shiga toxin, which causes dysentery. Because the outside of our cells are flat and covered with sugars, these 2-D nanosheets can effectively mimic cell surfaces.

>Read more on the Advanced Light Source website

Image: A molecular model of a peptoid nanosheet shows loop structures in sugars (orange) that bind to the Shiga toxin (shown as a five-color bound structure at upper right).
Credit: Berkeley Lab

The search for an Ebola vaccine

The search for an Ebola vaccine

Researchers expertly solved the crystal structures of drugs bound to the outer coating of the Ebola virus to pinpoint the regions that are essential for inhibitory activity.

Ebola is a viral disease that is highly infectious and associated with a high risk of death. It first arose in 1976, from which point it was associated with dozens of small-scale outbreaks; however, in 2013 Ebola was responsible for a huge epidemic in West Africa. Emergency was declared and over 11,000 people lost their lives to the virus. Despite this horrific state of affairs, Ebola still remains an untreatable disease and there is no vaccine to prevent infection.

>Read more on the Diamond Light Source website

 

World Polio Day

World Polio Day

Are we nearing the end of the war on polio?

There was a time when the word itself was enough to strike fear into the hearts of people around the world. Polio: a highly infectious virus that could shatter young lives in the blink of an eye. On the 24th of October, we mark World Polio Day, and this is something worth celebrating. Because whilst the story isn’t over yet, it may well be nearing its end.

Polio has been around since before records began, but it wasn’t until the early-twentieth century that epidemics began to sweep through communities in Europe and America, affecting many thousands of children and families.

It’s hard to underestimate the terror once caused by polio. At its height in the 1950s, parents routinely lived in fear of their children becoming quarantined, paralysed or even worse. It was a dark time in medical history but, despite this, polio really is a success story for modern science.

>Read More on the Diamond Light Source website

Molecular Movie

Molecular Movie

Researchers Create Molecular Movie of Virus Preparing to Infect Healthy Cells

With SLAC’s X-ray laser, scientists captured a virus changing shape and rearranging its genome to invade a cell.

A research team has created for the first time a movie with nanoscale resolution of the three-dimensional changes a virus undergoes as it prepares to infect a healthy cell. The scientists analyzed thousands of individual snapshots from intense X-ray flashes, capturing the process in an experiment at the Department of Energy’s SLAC National Accelerator Laboratory.

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