Prioritised support from ESS and MAX IV produces SARS-CoV-2 research results

Prioritised support from ESS and MAX IV produces SARS-CoV-2 research results

15 MAY 2020

Left: Photo of crystallization drop showing many hexagonal-shaped crystals of SARS CoV-2 Nsp10. Right: Single crystal of Nsp10 frozen on a 0.08mm loop (BioMAX beamline, MAX IV). Courtesy of MAX IV and ESS.

An international collaboration between the UK’s UCL School of Pharmacy, Lund Protein Production Platform at Lund University, and the European Spallation Source has initiated bio-physical and structural studies of three non-structural proteins from the novel coronavirus, SARS CoV-2, the causative agent of COVID-19.

The Deuteration & Macromolecular Crystallisation (DEMAX) platform at ESS has been offering prioritised access to laboratory services for scientists and researchers working on COVID-19-related research projects. Under this call, a research project on viral proteins was accepted and the research team recently managed to solve, and have now started to analyse, one of these proteins, Nsp10, with the help of the BioMAX beamline at MAX IV Laboratory.

Ribbon diagram of SARS CoV-2 Nsp10 in its unbound form. Nsp10 contains two zinc fingers (zinc ions are shown as grey spheres). Courtesy of UCL/LP3/ESS

The ultimate goal for this research project is to obtain high resolution X-ray crystal structures of these proteins alone or in complex with each other to enable the search for small molecule inhibitors that disrupt their activity. These structural studies will also be complemented with other biophysical characterisation experiments such thermal stability, microscale thermophoresis and solution scattering studies using X-rays and neutrons.

According to Dr. Zoë Fisher, group Leader for DEMAX at ESS, “Neutron protein crystallography of these viral proteins in complex with inhibitors can reveal atomic-level details of hydrogen atoms and binding interactions that could be crucial for understanding—and potentially improving on—inhibitor binding. Small-angle scattering of different complexes of these proteins in solution could also help us to understand the behaviour and shape of the molecules under physiological conditions. “

This project is an international collaboration between Prof. Frank Kozielski (Main PI, School of Pharmacy, University College London), Dr. Wolfgang Knecht (Lund Protein Production Platform (LP3), Lund University) and Dr. Zoë Fisher (DEMAX, European Spallation Source ERIC, Lund).
It is supported by the MAX IV rapid access call COVID-19, and the ESS DEMAX call for prioritised projects related to COVID-19 research.

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