DOE labs help drive global effort to fight COVID-19 with physics
Although most basic research has been suspended by the coronavirus pandemic, some labs remain open to engage in a furious effort to find treatments for the disease. Physicists, chemists, and their analytic tools are vital to a key part of that quest: decoding the three-dimensional structures of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and finding locations where drugs could latch on and disable the viral machinery. The virus itself is not used for those experiments, only the cloned proteins that are its principal working parts.
As of early April, in the US, at least 23 groups were working at the Advanced Photon Source at Argonne National Laboratory as of press time, according to Bob Fischetti, life sciences adviser at the APS. The National Synchrotron Light Source II at Brookhaven National Laboratory, SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), and the Advanced Light Source at Lawrence Berkeley National Laboratory are operating with minimal staff, each keeping open several x-ray protein crystallography beamlines strictly for coronavirus research.
Outside the US, the life sciences beamlines were open for SARS-CoV-2 research at the UK’s Diamond Light Source.The BESSY II light source in Berlin closed briefly but resumed operations on 2 April for coronavirus research, which is also ongoing at the Shanghai synchrotron in China, where the first 3D structure of the main protease protein was resolved. Officials there did not respond to requests for comment. The European Synchrotron Radiation Facility in France has been closed for an upgrade, but it announced in early April that it would consider reopening beamlines on a case-by-case basis for coronavirus research.
Structures of many of the virus’s 28 or 29 proteins (estimates vary on the exact number) have been resolved, both alone and in complexes with various molecules, known as ligands, that bind to them. Among those resolved structures are the main protease (Mpro), an enzyme that processes long viral polyproteins into shorter functional units; an endoribonuclease called Nsp15; and the spike protein that protrudes from the coronavirus surface and initiates infiltration to human cells.
As of 25 March, 108 structural determinations of SARS-CoV-2 proteins, both alone and with attached compounds, had been deposited in the open-access Worldwide Protein Data Bank (PDB). At that time, 77 structures of Mpro, with various ligands, had been submitted by teams working at the Diamond Light Source. More structures were expected to be released in mid-April.
Several scientists caution that some of the deposited structures are not very well defined. “Fast and automated does not always mean good quality,” says Andrzej Joachimiak, who heads a crystallography group at the APS. Crystallographers traditionally deposit structures in the PDB before their research has been refereed, notes John Helliwell, a retired University of Manchester biophysicist, chemist, and crystallographer.
Read more from Physics Today: https://physicstoday.scitation.org/doi/full/10.1063/PT.3.4470