New targets for antibodies in the fight against SARS-CoV-2

An international team of researchers examined the antibodies from a large cohort of COVID-19 patients. Due to the way antibodies are made, each person that is infected has the potential to produce many antibodies that target the virus in a slightly different way. Furthermore, different people produce a different set of antibodies, so that if we were to analyse the antibodies from many different patients, we would potentially be able to find many different ways to neutralise the virus.

The research article in the journal Cell is one of the most comprehensive studies of its kind so far. It is available online now and will be published in print on 15 April. These new results now show that there are many different opportunities to attack the virus using different antibodies over a much larger area than initially thought/mapped.

Professor Sir Dave Stuart, Life Sciences Director at Diamond and Joint head of Structural Biology at the University of Oxford, said:

SARS CoV-2 is the virus that causes COVID-19. Once infected with this virus, the human immune system begins to fight the virus by producing antibodies. The main target for these antibodies is the spike protein that protrudes from the virus’ spherical surface. The spike is the portion of the virus that interacts with receptors on human cells. This means that if it becomes obstructed by antibodies, then it is less likely that the virus can interact with human cells and cause infection.

By using Diamond Light Source, applying X-ray crystallography and cryo-EM, we were able to visualise and understand antibodies interact with and neutralize the virus. The study narrowed down the 377 antibodies that recognize the spike to focus mainly on 80 of them that bound to the receptor binding domain of the virus, which is where the virus spike docks with human cells.

Read more on the Diamond website

Image: Figure from the publication showing how the receptor binding domain resembles a human torso.

Credit: The authors (Cell DOI: 10.1016/j.cell.2021.02.032)

Science Begins at Brookhaven Lab’s New Cryo-EM Research Facility

Brookhaven Lab’s Laboratory for BioMolecular Structure is now open for experiments with visiting researchers using two NY State-funded cryo-electron microscopes.

UPTON, NY—On January 8, 2021, the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory welcomed the first virtually visiting researchers to the Laboratory for BioMolecular Structure (LBMS), a new cryo-electron microscopy facility. DOE’s Office of Science funds operations at this new national resource, while funding for the initial construction and instrument costs was provided by NY State. This state-of-the-art research center for life sciences imaging offers researchers access to advanced cryo-electron microscopes (cryo-EM) for studying complex proteins as well as the architecture of cells and tissues.

Many modern advances in biology, medicine, and biotechnology were made possible by researchers learning how biological structures such as proteins, tissues, and cells interact with each other. But to truly reveal their function as well as the role they play in diseases, scientists need to visualize these structures at the atomic level. By creating high-resolution images of biological structure using cryo-EMs, researchers can accelerate advances in many fields including drug discovery, biofuel development, and medical treatments.

Read more on the BNL website

Image: Brookhaven Lab Scientist Guobin Hu loaded the samples sent from researchers at Baylor College of Medicine into the new cryo-EM at LBMS.

The African fly of death might also save lives

For the first time, an international team of scientists recreated in the lab the molecule that allows the tsetse fly to feed on blood. It’s a powerful yet small anticoagulant with a unique and strong binding to thrombin, the key enzyme of the coagulation pathway. X-ray diffraction measurements at two synchrotron facilities ––ALBA and ESRF–– were instrumental to understand the structure and the mechanism of action of this molecule, which suggests it is also a promising platform for designing improved anticoagulant drugs.

 In the waiting rooms of health care facilities around the world, millions of patients take anticoagulants every day. These are life-saving drugs for the treatment of cardiovascular diseases, which now are also being explored for their benefits to patients with advanced symptoms of COVID-19.

And, as incredible as it may seem, the tsetse fly, responsible for the sleeping sickness disease in humans, is now on the spotlight in the efforts to develop more powerful and safer anticoagulants. 

In a study co-authored by Bárbara Calisto, researcher at the ALBA Synchrotron, an international team of scientists has become the first to recreate in the lab the molecule that the tsetse fly uses to prevent coagulation when it bites to feed. These bites are also the entry channel for the parasite that causes sleeping sickness, a life-threatening disorder, if untreated. And the reason why the tsetse fly has been dubbed as the fly of death in Africa.

Read more on the ALBA website

Image:  Bárbara Calisto at the XALOC beamline of the ALBA Synchrotron

Credit: ALBA

Scientists discover potential method to starve the bacteria that cause Tuberculosis

By deepening our understanding of how Tuberculosis bacteria feed themselves, University of Guelph researchers have identified a potential target for drug treatment. The team used the Canadian Light Source (CLS) at the University of Saskatchewan to image the bacteria in fine detail.

The infectious disease Tuberculosis (TB) is one of the leading causes of death worldwide. While rates of TB in Canada have remained relatively static since the 1980s, the disease disproportionately affects Indigenous populations. With TB-causing bacteria becoming increasingly resistant to antibiotics, researchers and drug makers are eager to find new, more effective treatments.

Researchers have known for some time that the bacteria that causes TB (Mycobacterium tuberculosis) uses our body’s cholesterol – a steroid – as a food source. Other relatives of the bacteria that do not cause disease share its ability to break down steroids. In this study, the University of Guelph team identified the structure of an enzyme (acyl CoA dehydrogenase) involved in steroid degradation in another member of the same bacteria family, called Thermomonospora curvata.

Read more on the CLS Website

Image: This rendering shows the shape of a tunnel (orange) where the substrate binds. Any drugs targeting this enzyme would need to fit to this pocket.

Visualising the bionanomachines that create potent antibiotics

… and other modern drugs.

Researchers from McGill University and Yale University used the Canadian Light Source (CLS) at the University of Saskatchewan to make a discovery that could help design future therapeutic drugs. The research team studied how mega-enzymes, known as nonribosomal peptide synthetases (NRPSs), create potent antibiotics, immunosuppressants and other modern drugs.

In a paper featured on the cover of the May 2020 issue of Nature Chemical Biology, the team reports how they were able to visualize an NRPSs’ mechanical system using the CMCF beamline at the CLS.

>Read more on the Canadian Light Source website

Image: Associate Professor Schmeing in the lab