Bristol researchers find a potential ‘game changer’ in the fight against COVID-19

By Edward Deacon, SciTech Digital Editor

Researchers at the University of Bristol have found a method that could stop coronavirus infecting human cells, after identifying a ‘druggable pocket’ in the SARS-CoV-2 Spike protein.

The exterior of SARS-CoV-2 molecules are covered in many glycoproteins, ‘Spike proteins’, which have been found to contain a ‘pocket’ capable of being targeted with anti-viral drugs that could eliminate the virus.

These Spike proteins are critical to the infectivity of the virus, as they bind to human cells, allowing the virus to replicate and bring harm to the host.

Utilising electron cryo-microscopy – an imaging technique that uses an electron microscope on samples cooled to cryogenic temperatures – the Spike proteins were able to be analysed at a near atomic resolution.

The study, led by Prof. Christiane Schaffitzel from the School of Biochemistry, and Prof. Imre Berger from the Max Planck-Bristol Centre for Minimal Biology, used a 3D model to analyse the structure and molecular composition of the Spike protein.

This then allowed the researchers to discover that linoleic acid (LA), was found buried in the ‘pocket’ within the Spike protein.

By having these pockets, the Spike proteins are capable of binding to LA molecules in the human body, and disrupting cellular functions, including maintaining cell membranes in the lungs, and affecting inflammation and immune modulation, which are key features of the disease’s progression.

In the past, rhinovirus (a virus causing the common cold) was found to have a similar pocket that was exploited to create molecules that distorted the structure of the virus and reduce infectivity.

The Bristol team are optimistic a similar strategy can be implemented against SARS-CoV-2 to develop anti-viral drugs that target the pocket in the Spike proteins.

Discussing the implications of the study, Prof. Schaffitzel commented: ‘In the absence of a proven vaccine, it is vital that we also look at other ways to combat the disease.

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‘If we look at HIV, after 30 years of research what worked in the end is a cocktail of small molecule anti-viral drugs that keeps the virus at bay.

‘Our discovery of a druggable pocket within the SARS-CoV-2 Spike protein could lead to new anti-viral drugs to shut down and eliminate the virus before it entered human cells, stopping it firmly in its tracks.’

Professor Berger added: ‘Our discovery provides the first direct link between LA, COVID-19 pathological manifestations and the virus itself. The question now is how to turn this new knowledge against the virus itself and defeat the pandemic.’

Featured Image: University of Bristol

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