Beamlines, proteins, and a national synchrotron — a Pandemic Pioneer’s hunt for a COVID treatment

Daren Fearon, Beamline Scientist, Diamond

We’re looking at Harwell’s Pandemic Pioneers, the scientists and innovators based at Harwell Campus who are helping us all build back better. First up in our series is Daren Fearon, a chemical biologist and ‘beamline scientist’ who works at Diamond Light Source — the UK’s national synchrotron facility. Daren’s soft-spoken Glaswegian demeanour cloaks the global significance of the work he and the XChem team are doing to help investigate the protein building blocks which are crucial not only to our current COVID vaccines, but to an eventual treatment for the virus.

“Everyone has a different name for it. ‘The Spaceship’ comes up a lot. You can see it from the A34, just about. I don’t think a lot people realise what it is. There is a particle accelerator just hanging around in the Oxford countryside.”

The aforementioned ‘Spaceship’, or synchrotron to give its proper name, sits at the heart of The Harwell Science and Innovation campus just outside Oxford. A gleaming futuristic ring 562m in circumference it’s the only synchrotron in the UK, and the elite teams of scientists who use it have a vital role to play in the quest for a Covid-19 treatment.

“We use it to accelerate electrons at pretty much the speed of light. When you do that they can emit rays of light 10 billion times brighter than the sun. We can use these very intense x-rays to study all sorts of materials, including protein crystals which is where I come in.”

So says Daren Fearon, a 34-year-old ‘beamline scientist’ who’s been working at Diamond Light Source (the official name for the national synchrotron) since the first days of the outbreak.

Fearon and the XChem team — “yes it does sound a bit like ‘X Men’” smiles Fearon — have used its synchrotron technology to produce thousands of images of seven key Covid proteins in pursuit of a potential treatment.

“When I started on 2nd February last year coronavirus was in the news but it hadn’t quite hit these shores. But within two weeks my boss said some collaborators at Diamond had produced crystals for one of the proteins. So we used our platform to carry out what we call a fragment screen where we tried to identify really small molecules that bind to the Covid-19 virus. Then you can figure out ways to combine these molecules to make a drug.”

Although vaccines have recently dominated the headlines, Fearon and his fellow biologists’ second front in the Covid battle may prove equally decisive.

“Vaccines are prophylactic, they prevent you getting the disease. Antivirals are something you would take once you have it — to cure or treat it. Some of the poorer countries and other parts of the world don’t have a big supply of vaccines. And a lot of the vaccines that have been developed so far have very specific storage conditions, you need to keep them at -80°C which makes them hard to get to some people.”

Fearon and the XChem team, in collaboration with scientists from the UK, the US and Brazil, have identified “seven Covid proteins that are potentially druggable.” This refers to proteins particularly prone to bind with high affinity to a drug.

“We’re not finding drugs directly but we’re essentially finding the building blocks” says Fearon. “Like little LEGO blocks, we just have to figure out how to stick them together afterwards.”

“We literally put a single protein crystal which we’ve dipped in solution and that contains these kind of bricks to make up the drugs. Then we rotate the crystal in front of the beam of x-rays, and by collecting how the x-rays are scattered we can build a 3D model of the protein and contextualise how these building blocks interact with it.”

The nerve centre of the operation is a small room affectionately named ‘The Hutch’, where groups of three or four scientists operate and monitor sophisticated robots. The information is then fed to an adjoining Data Processing Centre where the number-crunching occurs.

XChem are one of the founding partners of the Covid Moonshot global crowdsourcing initiative, which aims to accelerate the development of an antiviral with no IP constraints.

“Anything Diamond has been the lead on we make open access. We’re still developing these compounds, but we’re pretty close to sending something into pre-clinical trials. And that involved people from 30 different places around the world. People working for free or just at cost, because of how important everything is. So hopefully a future drug can be made as cheaply as possible in the same way many generic drugs are.”

So a multinational won’t come in and monetize it for themselves?

“Exactly.”

Synchrotron aside, the Harwell campus itself has proven a useful resource.

“There’s a facility called the Research Complex at Harwell, they’re mainly life sciences and chemistry. None of our Covid research would have been possible without using their equipment, so it’s key to have facilities and collaborators like that on site.”

Alas, according to Fearon, those hoping for a headline-grabbing ‘Eureka’ moment are likely to be disappointed.

“The vaccine development for this coronavirus has been amazingly fast. General drug discovery has a slower pace. There are a couple of things just entering clinical trials now. But the trials are quite lengthy.”

However the chemical biologist is hopeful patience might bring its own rewards.

“No one knew the vaccine was going to work at first, there were no guarantees. If you look at HIV and other viruses we’ve not been able to develop a vaccine for those. Also, there will be future pandemics where this could help. If we have an antiviral that works against coronaviruses in the next pandemic, when they’re taking the year to develop that vaccine, hopefully they could have a drug to provide to patients in the meantime.”

And the dream scenario?

“All going swimmingly, a treatment that can help patients in the next few years and is effective against other related coronaviruses.”

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