Institut Laue Langevin publishes new findings on SARS-CoV-2 infection mechanisms

Neutron reflectometry reveals SARS-CoV-2 spike protein induces lipid stripping from cell membrane
22nd July 2021
ILL Covid study

Grenoble, France, 22th July 2021 / Sciad NewswireScientists at the Institut Laue-Langevin (ILL), in collaboration with the Paul Scherrer Institut (PSI), the Institut de Biologie Structurale (IBS) and the Australian Nuclear Science and Technology Organisation (ANSTO), have published new data on how the SARS-CoV-2 spike protein interacts with mammalian lung cell membranes allowing the viral RNA to enter human cells. The purpose of the SARS-CoV-2 spike protein is relatively well understood. The glycoprotein is responsible for the fusion event that allows the virus to enter human cells and cause infection and, for this reason, it has been the focus for most COVID-19 vaccines.

“A lot of research has focused on the interaction between the virus spike protein and the angiotensin-converting enzyme 2 (ACE2) for which there are many receptors on cell surfaces in the lungs,” explains Prof Giovanna Fragneto, Large Scale Structures Group Leader at ILL. “What is less well understood is how the spike protein interacts with the rest of the cell membrane. Our expertise in creating model cell membranes and the enormous resolving power offered to us by neutron reflectometry meant that we were uniquely positioned to explore these wider interactions.”

The team produced systems that excluded some of the proteins found in real cell membranes so that the individual contribution of each component could be more easily understood. “Our observations surprised us at first,” states Prof Fragneto. “We saw an unexpected large change in the composition of the lipid bilayer, compatible with an increase of water content, as soon as we introduced the stable spike protein (sSpike) and we saw this with and without the presence of soluble ACE2. Combining this information with the previous knowledge that lipid pockets can stabilise the spike protein closed structure, we concluded that sSpike is able to significantly strip away lipids from the cell membrane, disrupting and potentially entering directly through the membrane.”

“The fact that we can observe these interactions is a great accomplishment,” explains Dr Samantha Micciulla. “Until recently, it just hasn’t been possible to create complex model cell membranes and investigate structural interactions at the nanometre level. Neutron reflectometry allows us sub-nanometre levels of resolution, enabling differentiation even between different atomic isotopes, so we can fully interrogate the molecular interactions between sSpike and different elements of the membrane.”

Prof. Fragneto concludes: “While it is clearly important for research to focus on the interaction between ACE2 and the spike protein, our observations indicate a wider field of interest. This direct interaction with the lipid bilayer on the cell surface could provide insight for the development of more effective therapeutics or future vaccines. Of course, this is fundamental research, and we are far from using this in a pharmaceutical application; however, this study provides additional understanding that will be important to virology studies in the future, for SARS-CoV-2 and beyond.”

References

https://www.nature.com/articles/s41598-021-93996-x

ENDS

For further information contact:

ILL contact: Prof Giovanna Fragneto

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Notes to editors:

About the ILL 
Institut Laue-Langevin is an international research centre based in Grenoble, France. It has led the world in neutron-scattering science and technology for almost 50 years, since experiments began in 1972. ILL operates one of the most intense neutron sources in the world, feeding beams of neutrons to a suite of 40 high-performance instruments that are constantly upgraded. Each year 1,200 researchers from over 40 countries visit ILL to conduct research into condensed matter physics, (green) chemistry, biology, nuclear physics, and materials science. The UK, along with France and Germany is an associate and major funder of the ILL. www.ill.eu