6 7 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 2 1 / 2 2 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 2 1 / 2 2 Supporting International COVID-19 Research D iamond Light Source has continued to give international COVID-19 researchers highpriority access to beamtime throughout the year, despite lockdown restrictions around theworld. Over the year, 530 shiftswere delivered across all instruments for COVID-19 research. The work taking place at Diamond is grouped into those projects developing understanding of the virus structure and function, new vaccinedesignandefficiency, drugdevelopment (includingbothnewdrugs and re-purposingexistingdrugs) anddevelopingnewtherapies. Understanding how the virus operates Several studies have continued to develop detailed understanding of the SARS-CoV-2 viral mechanisms and structure. These significant and rapid fundamental research efforts have already resulted in the licensing of several vaccines which have been rolled out tomanymillions around theworld in rapid vaccination programmes. In addition, neutralising monoclonal antibodies (mAbs) have been developed to be used prophylactically or therapeutically. A research group led by Professor Peijun Zhang (Director of the Electron Bio-Imaging Centre (eBIC) at Diamond and Professor of Structural Biology at the University of Oxford) have continued their work on unlocking the structure of the SARS-CoV-2 virus 1 . The research team used the cryo-electron microscopy (cryo-EM) facilities at eBIC to investigate viral replication in a Vero cell line under near-native conditions. They reported critical structural events such as viral RNA transport portals and native virus spike structures. Their approach gave a holistic view of SARS-CoV-2 infection from the whole cell to individual molecules and the study results validated previous findings from studies using electron microscopy on plastic-embedded samples. The study further expands knowledge on viral assembly and egress of SARS-CoV-2 as well as its presence in other membrane compartments. It also confirms the value of cryo-EM and soft X-ray tomography as techniques to investigate whole cell morphology with the advantages of frozen-hydrated conditions and fast sample preparation. Professor Jonathan Grimes (Diamond Fellow and Professor of Structural Biology at the University of Oxford) worked in collaboration with a number of University colleagues on two projects studying coronavirus mechanisms. The first aimed to improve understanding of the mechanism of coronavirus RNA capping which, though an important feature of the viral life cycle, is poorly understood 2 . Using numerous assay techniques, the group demonstrated the vital function of the nucleotidyltransferase (NiRAN) domain of SARS-CoV-2 non-structural protein 12 (nsp12) in viral synthesis. They also showed that this activity can be inhibited by remdesivir triphosphate which highlights the NiRAN domain as a possible target for repurposed antiviral drugs. In the second study Professor Grimes was part of a group performing further characterisation of the virus using biochemical techniques 3 . Image of Beamline I03. Crystals of the RBD protein. The Titan Krios is a state-of-the-art fully automated electron microscope designed for rapid, stable, high-resolution data collection on frozen-hydrated samples.