Supporting research on Covid-19

A lot of action in the virus’s life cycle happens at the surfaces. Like a space ship docks onto a space station the virus has to hook onto the cell it intends to infect and create an interlock for dumping its genetic material. In the specific case of SARS-CoV-2, which looks very much like a sea mine, the proteins of the spikes dock onto the epithelial cells in the patient’s airways by binding a special enzyme (ACE2) expressed – and therefore present - on those cells’ surface.

A considerable part of research on SARS-CoV-2 will be targeting these docking processes. Neutron reflectometry, which is the neutron technique sensitive to surfaces, can tell you how it happens - like in the case of the hepatitis C virus research performed in 2017. ILL possesses a top-of-the-range reflectometry suite and outstanding expertise in applying this suite to the study of membrane systems.

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Neutron crystallographyis one of the indispensable modern analytical tools for obtaining insight into the life cycle of viruses.
In simple terms, crystallography provides us with three-dimensional pictures of the various biochemical engines that the virus relies upon for reproduction. If these engines can be blocked through appropriate medication e.g. by introducing a molecule into the site where the biochemical action takes place, then the viral disease can be cured.

Many of these engines manipulate hydrogen nuclei. This is where the neutrons come in. They are ideal for detecting hydrogen nuclei in the structure. The ILL is the leading neutron facility in the domain of biological macromolecular neutron crystallography. Recent studies on HIV-1 protease (a biochemical engine that - like a pair of scissors - cuts long polymer chains and is essential for the life-cycle of the HIV virus) performed at the ILL’s instrument LADI perfectly illustrate the case. The neutron data allows to better design the drug that blocks the scissors in their active site.

SARS-CoV-2 offers many potential targets for such neutron studies. Given the relevance of this research, ILL has decided -in the framework of the Endurance upgrade programme- to enhance capacity by adding another instrument (DALI) (pdf - 2.36 Mi) to its instrument suite. DALI was just in the process of being assembled when the lock-down hit the ILL activities. The installation will be completed after the lock-down and the instrument will be commissioned during the next cycle.

When it comes to studying the function of larger biological complexes such as assembled viruses, small angle neutron scattering becomes an important analytical tool. This is due to the fact that: the larger the objects under investigation, the smaller gets the angle of deviation of the neutrons during scattering from those objects. Neutrons offer the enormous advantage that individual subunits can be marked by advanced deuteration allowing to distinguish specific regions (RNA, proteins and lipids) in the complexes.

While NMR and cryo-electron microscopy provide the detailed atomic-resolution structure of small biological assemblies, neutron scattering allows researchers to pan back to see the larger picture of full molecular complexes at lower resolution. Neutron scattering is also uniquely suited to determining the structure of functional membrane proteins in physiological conditions. Neutron scattering will therefore make it possible to map out the structure of the complex formed by the SARS-CoV-2 spike protein—the protein surrounding the virus—and its human receptor.

With its excellent suite of small-angle instruments and the outstanding expertise in applying them to biological systems, ILL is perfectly positioned for performing such studies on SARS-CoV-2.

More about Small Angle Neutron Scattering

Finally, we should not forget that viruses in their physiological environments are highly dynamic systems. Knowing how they move, deform and cluster is essential to the optimisation of diagnostic and therapeutic processes. Neutron spectroscopy, which is ideally suited to follow the motion of matter from the small chemical group to large macromolecular assemblies, is the tool of choice to provide this information. 

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