Nanobodies hold the key to imaging COVID-19

Researchers from Protein Production UK, a collaborative project led by The Rosalind Franklin Institute, have isolated nanobodies – a type of antibody used in research, which bind to the ‘spike’ protein of the SARS-CoV-2 virus.

The team have already made these nanobodies, which bind with high affinity to the ‘spike’ protein, available to researchers at The University of Oxford. They will be making these important research tools widely available to other research groups around the world.

Nanobodies are antibodies found in camelids (llamas, alpacas and camels), which are much smaller than human antibodies. Their high stability, small structure, and specificity makes them ideal for the purification and stabilisation of proteins and protein structures, prior to imaging.

The team at The Franklin are targeting their work at a protein which sits on the outside of the SARS-CoV-2 viral particle known as the ‘spike’, which binds to human cells during an infection. This protein has a specific area – the receptor binding domain (RBD) – which is responsible for this binding action. The protein is a major target in COVID-19 research, as it plays a pivotal role in infection and may be a strong target for future vaccines and therapies.

Nanobodies can stabilise the ‘spike’ to enable better imaging at the atomic scale, using advanced imaging techniques including cryo-electron microscopy (cryo-EM). The nanobodies also enable the RBD to be stabilised bound to its target, helping researchers better understand how it behaves in the body, and how it might interact with new drugs.

The team are also investigating whether the nanobodies they identify, or therapies derived from them, could be used to create highly specific ‘blockers’, which could contribute to treatments for COVID-19, by preventing the SARS-CoV-2 virus from binding to human cells and causing infection. There is also potential in nanobodies for diagnostics, creating highly efficient and quick tests.

Professor James Naismith, Director of the Rosalind Franklin Institute explains: “”One single protein often has multiple target sites (epitopes) for the human immune system to produce antibodies to bind to. When antibodies bind to certain epitopes they ‘neutralise’ the virus, this prevents further infection thus stopping the virus in its tracks. The tools that PPUK, a model for multi-partner collaborations, will make available will be helpful to scientists working on SARS-CoV-2 virus.”

Identifying which nanobodies have ‘binding’ and which have ‘binding and neutralising’ actions is a key next step for the group, and one which will see them search for a wider range of nanobodies, and compare their action to human antibodies derived from patient samples.

Professor Ray Owens, who leads Protein Production UK for The Franklin, says: “There is an unprecedented level of team-work and collaboration globally to image, understand, and treat COVID-19. We are working with colleagues at the University of Oxford to use the nanobodies developed here at The Franklin, to gain insights into the structure of the virus that causes COVID -19”

The Rosalind Franklin Institute is a new national research institute, funded by UK Research and Innovation through the Engineering and Physical Sciences Research Council. Its mission is to develop and apply disruptive new technologies in the physical and engineering sciences to transform the UK’s life science research and pharma sector.

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Notes to editors:

About Protein Production UK

Protein Production UK (PPUK) is a project hosted by The Rosalind Franklin Institute in partnership with Diamond Light Source, the UK’s national synchrotron light source, (http://www.diamond.ac.uk), and is tasked with devising new ways to deliver ‘the right sample, at the right time, for the right experiment’. This involves improving existing technology and developing new methods, that will, enable the structural biology community to keep pace with the rapidly expanding range of tools available for analysis, using X-rays and electrons.

PPUK has established the nanobody discovery platform in The Franklin’s Structural Biology Theme, and the rapid production of these reagents for Covid 19 work by PPUK is proof of the strategic importance of such a facility in the UK.

PPUK is currently based at the Research Complex at Harwell http://www.rc-harwell.ac.uk

Diamond Light Source have created a page dedicated to their world leading research on COVID-19 – https://www.diamond.ac.uk/covid-19.html.

More information about Structural Biology Facilities across Europe focused on research into Covid 19 is available on https://instruct-eric.eu/covid19.

The Rosalind Franklin Institute

The Rosalind Franklin Institute is a national institute dedicated to transforming life science through interdisciplinary research and technology development. The Institute will bring together researchers in life, physical science, and engineering, to develop disruptive new technologies designed to tackle major challenges in health and life sciences. Focussing initially on five major research themes, the Institute will have significant impact in imaging, diagnostics, drug development, and many more fields.

The Franklin is funded through the UK Research and Innovation through the Engineering and Physical Sciences Research Council (EPSRC). The Institute is an independent organisation founded by the UK Research and Innovation, ten UK universities, and Diamond Light Source, and will have its central hub at the Harwell Campus.

The Rosalind Franklin Institute is a company limited by guarantee registered in England and Wales, registration number 11266143. We are a Registered Charity, number 1179810.

Twitter: @RosFrankInst
http://www.rfi.ac.uk

The Engineering and Physical Sciences Research Council (EPSRC)

The EPSRC is the main funding body for engineering and physical sciences research in the UK. By investing in research and postgraduate training, we are building the knowledge and skills base needed to address the scientific and technological challenges facing the nation.

Our portfolio covers a vast range of fields from healthcare technologies to structural engineering, manufacturing to mathematics, advanced materials to chemistry. The research we fund has impact across all sectors. It provides a platform for future UK prosperity by contributing to a healthy, connected, resilient, productive nation.

EPSRC is part of UK Research and Innovation, a new body which works in partnership with universities, research organisations, businesses, charities, and government to create the best possible environment for research and innovation to flourish. We aim to maximise the contribution of each of our component parts, working individually and collectively. We work with our many partners to benefit everyone through knowledge, talent and ideas. For more information visit UK Research and Innovation.

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Laura Holland
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