Posted on 27 April 2020
Ongoing work in York during the global COVID-19 pandemic, led by Professor Fred Antson, aims to determine a high resolution structure of an important protein in the SARS-CoV-2 virus. Achieving this would provide detailed information about how this virus assembles and replicates.
Left, illustration of SARS-CoV-2 virion in cross-section, with nucleocapsid protein coloured blue. Right, negatively stained transmission electron micrograph showing a nucleocapsid assembly, produced by researchers in YSBL (scale bar 100nm). Image credit: Jake Smith, Oliver Bayfield.
Much work globally has focused on the ‘spike’ proteins on the exterior of the virus, but the protein of interest to the team in York is the nucleocapsid protein (highlighted in blue in the image). This protein binds to the viral RNA forming a long helix-like assembly that is condensed inside the virus particle, safeguarding the RNA from degradation.
The researchers had the relevant gene synthesised in early March, and started working on protein expression and characterisation just as the UK was going into lockdown.
A high resolution structure of the nucleocapsid protein assembly could help in the development of antiviral drugs that disrupt the protein-protein or protein-nucleic acid interactions that are critical for virus assembly.
This may allow the development of drugs to treat not only COVID-19, but also SARS-CoV and MERS-CoV, as well as other related coronaviruses that may emerge in the future.
The team, consisting of Postdoctoral Researcher Dr Oliver Bayfield and PhD students Dorothy Hawkins and De-Sheng Ker have been working in shifts around the clock so that they can follow social distancing guidelines whilst maximising the progress of their research.
Virus researchers, Dorothy Hawkins, Oliver Bayfield and De-Sheng Ker (left to right) discuss progress.
The researchers are collaborating with Dr Becky Thompson, the cryo-electron microscopy facility manager and senior support scientist at Leeds. With Becky, they are collecting the vital high-resolution microscopy data on the protein and protein-RNA complexes produced in York.
The team have also been sending purified protein and the gene that encodes several protein constructs produced at York, to labs in Sheffield, Oxford, and London. These materials are playing an important role in helping develop antibody tests for COVID-19 that will ultimately determine who has been infected with the disease.
Since starting work on SARS-CoV-2, the team have received messages and offers of support from colleagues across the University, and have been receiving enquires about collaboration almost daily. The work shows how scientists can very rapidly contribute to enhancing understanding in the face of a global pandemic, and is something very positive for science that is emerging from this troubling time.