Diamond Light Source is the UK’s national synchrotron, providing industrial and academic user communities with access to state-of-the-art analytical tools to enable world-changing science. Shaped like a huge ring, it works like a giant microscope, accelerating electrons to near light speeds, to produce a light 10 billion times brighter than the Sun, which is then directed off into 33 laboratories known as ‘beamlines’. In addition to these, Diamond offer access to several integrated laboratories including the Electron Bio-imaging Centre (eBIC) and the Electron Physical Science Imaging Centre (ePSIC).
Diamond serves as an agent of change, addressing 21st-century challenges such as disease, clean energy, food security and more. Since operations started, more than 14,000 researchers from both academia and industry have used Diamond to conduct experiments, with the support of approximately 700 world-class staff. More than 9,000 scientific articles have been published by our users and scientists.
Funded by the UK Government through the Science and Technology Facilities Council (STFC), and by the Wellcome Trust, Diamond is one of the most advanced scientific facilities in the world, and its pioneering capabilities are helping to keep the UK at the forefront of scientific research.
Some background to the work
Structural biology is now in the front line of responses to emerging virus diseases. This was first demonstrated in the development of drugs against HIV. In the years after AIDS was identified in the early 1980’s hundreds of structures were solved for several key viral enzymes with potential drug candidates, leading to the development of potent new compounds which are now part of effective therapy.
A key lesson was that even rapidly evolving RNA viruses can be checked by highly active multi-drug therapy. Another lesson was that the timescale for structure-guided discovery was long compared to the time for a pandemic to sweep the globe.
The COVID-19 outbreak is at a critical stage, the WHO suggest that China, through tough and effective containment has bought other countries more time. This is the third bat-derived coronavirus to cause outbreaks of human disease in less than 20 years, and the most serious. Meanwhile structural biology has been transformed by the impact of structural genomics and technology advances in both crystallography and cryo-EM.
Specifically in the area of drug discovery synchrotron automation has opened up ultra-high throughput screening methods like Xchem at Diamond.
Even so the response to COVID-19 has been remarkable: first reports of an unknown pneumonia were on 31st December 2019 and by 11th January, six virus sequences were made available. Structural biologists moved extraordinarily quickly, getting synthetic genes made immediately, rushing to pick them up the day they were finished, and in less than a month, on 5th Feb the first structure, of the main protease was released by the PDB, from Zihe Rao and Haitao Yang's team at ShanghaiTech. By then these coordinates had already been distributed by the team to 300 groups. In addition by this point, the protein had been used for in vitro assays and a collection of licenced drugs with potential antiviral activity had been identified and made available publicly.
Indeed by now 35 clinical trials have been started, with the first just closed, so the first results should start to emerge quickly. However, these are re-purposed compounds, the route to tailor made molecules will be longer.