CryoPowerEnvironment & Climate

How has cryo-EM helped identify the structure of SARS-COV-2?

By April 14, 2020 No Comments

Scientific advances have enabled planet Earth to quickly identify the SARS-CoV-2 virus, which turned in to COVID19.

Despite the fact there is currently no vaccine & the entire global scientific community are working feverishly to find currently available medicines to ease the symptoms of COVID19; we are some six months to a year away from a commonly agreed vaccine or proactively effective treatment.

As our Chief Medical & Chief Science Officer advise us regularly, COVID19 is a new disease, a new strain of the coronavirus family & as such we have never seen this type of infection or had to tackle it’s devastating wake.

However, one of the unique qualities of SARS-CoV-2, it’s very effective protein spike; was discovered by the process of cryo-electron microscopy (cryo-EM).

Cryo-EM is a technique pioneered by Jacques Dubochet of the University of Lausanne in Switzerland, Joachim Frank of Columbia University in New York City, US, & Richard Henderson of the MRC Laboratory of Molecular Biology in Cambridge, UK, for which they shared the 2017 Nobel Prize for Chemistry (1) & essentially is a form of transmission electron microscopy which allows for a specimen of interest to be viewed at cryogenic temperatures (2)

Cryo-EM uses samples which are usually frozen (frozen-hydrated) to preserve a specimen’s structure. A very thin slide of the specimen can be rapidly plunged into a liquid ethane bath (2) to vitrify the sample & which is then imaged by the electron microscope with low doses of electrons to minimize radiation damage (1)

The benefits of using cryo-EM technologies when imaging molecular biological samples, is the lack of need for dyes & crystallization to ensure a perfect image is obtained.

In the case of the SARS-CoV-2, thousands of images were taken using this technique, which then allowed a 3D printed image to be produced, identifying the protein spike we now know to cause such effective damage by the virus (3) These images were gathered in less than 24 hours & made the understanding of the virus structure globally understood.

With cryo-EM having only been recognised & gained broader adoption about seven years ago, advances in the electron detectors, software, productivity, and other important factors now allow researchers to resolve relevant biological samples at higher resolution quicker than ever before. With the use of the cryo-EM technology, the imagining sequence took a matter of hours, whereby without the use of the cryo-EM, it could have taken months even years to collate this valuable data. (4)

In the case of the SARS-CoV-2, Daniel Wrapp & Nianshuang Wang, University of Texas at Austin, US, & their colleagues were able to obtain the structure of an outer “spike” protein of SARS-CoV-2 which is believed to enable the new virus to force its way into host cells.

From harvesting the protein to submitting a paper to the journal Science on 10th February 2020, the process took just 12 days (1)

The speed with which the medical & scientific communities have worked to identify & recognise the structure of SARS-CoV-2 is astonishing & could have not been realised if it had now been for the use of the cryo-electron microscopy data. ThermoFisher Scientific identifies key dates in its publication ‘Cryo-EM Used in Novel Coronavirus Research to Support Vaccine, Treatment Development’ published 12th March 2020

  • January 6: The China Centers for Disease Control (NIVDC Institute) were able to confirm coronavirus pathogens, partly based on electron microscopy images taken with a Thermo Scientific Tecnai Spirit Transmission Electron Microscope (TEM). (4)
  • February 15:A team of researchers from the University of Texas at Austin and the National Institutes of Health (NIH) published a preprint in bioRxiv showing the first three-dimensional structure of the SARS-CoV-2 spike protein (S protein). (4)
  • February 19:Westlake Institute for Advanced Study in Hangzhou, China, showed success using their Krios G3i to capture the same SARS-CoV-2 spike protein bound to its human target, angiotensin-converting enzyme 2 (ACE2). ACE2 is the surface receptor for the coronavirus that interacts with the spike protein during infection. (4)
  • February 20: David Veesler’s group at the University of Washington School of Medicine published their structure of the coronavirus spike protein (4)
  • February 26: The spike protein structure from SARS-CoV-2 was made publicly available on the protein database. (4)

Structural biology has continued to advance at a record pace & therefore has allowed the scientific, medical & pharmaceutical experts to use date & structural information from applications such cryo-EM to develop effective medical testing of medicines & pharmaceuticals; with the ultimate aim of being able to vaccinate against such viruses as SARS-CoV-2, SARS, MERS & Zika.

Written by Katy-Jane Mason for & on behalf of Dolphin N2