As the global community works to contain the spread of the coronavirus disease (COVID-19) and treat those who have been diagnosed, there is an ongoing parallel fast-paced effort by researchers around the world to use cryo-electron microscopy (cryo-EM) to understand its infection of human cells. These cryo-EM researchers were able to determine the structure of SARS-CoV-2 spike protein and its cellular receptor during infection. In recent years, cryo-EM has become a popular and effective method for biological research – studying the structure of biologically important molecules like proteins and viruses at near-atomic resolution to better understand 3D structure and functionality. These findings will support and accelerate design of vaccines and the development of treatments for COVID-19. Researchers have made their structures from cryo-EM publicly available.
A computer rendering of a coronavirus, showing the characteristic “crown-like” glycoprotein spikes that inspired their name. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, belongs to this virus group (image courtesy of CDC).
What’s been done so far?
- 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).
- Throughout January: The Wuhan Institute of Virology, University of Hong Kong University, the U.S. National Institutes of Health (NIH), and others also obtained similar and complementary results with their Thermo Scientific TEMs. For example, the University of Hong Kong captured images showing the novel coronavirus replicating in cells. The Chinese Premier Li Keqiang visited the Institute of Pathogen Biology under the Chinese Academy of Medical Sciences in Beijing, China, and viewed an image of the coronavirus on a Thermo Scientific Tecnai TEM. During his visit, he commented that “accelerating research on how the virus is transmitted is key to preventing and controlling it.”
- 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). Mere days later the results were published in the peer-reviewed journal Science. Based on the SARS-CoV-2 genome sequence shared by Chinese researchers, they managed to prepare a purified sample of the spike protein and to determine its structure using single particle cryo-EM in less than two weeks. Like other coronaviruses, the latest SARS-CoV-2 uses spikes protruding from their surface to latch onto and enter cells. These researchers used a Thermo Scientific Krios cryo-TEM. “Figuring out the shape of the spike protein in SARS-CoV-2 is the key to figuring out how to target the virus,” said UT-Austin’s Jason McLellan in a LiveScience interview.
- 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. Their results, published in Science, could potentially inspire the development antibodies to block this critical interaction.
- February 20: David Veesler’s group at the University of Washington School of Medicine published their structure of the coronavirus spike protein, now available in Cell.
- February 21: The Vice Mayor of Shanghai visited our NanoPort microscopy facility in Shanghai to understand how our microscopy technology is helping the research community to understand the coronavirus and develop therapies for prevention and control.
- February 26: The spike protein structure from SARS-CoV-2 was made publicly available on the protein database.
Cryo-EM started gaining broader adoption about seven years ago as advances in the electron detectors, software, productivity, and other important factors allowed researchers to resolve relevant biological samples at higher resolution. In less than two months, significant progress has been made to understand the structure and behavior of the coronavirus. In the past, achieving this level of progress could have taken years. The team that mapped the spike protein used about 3,000 images which today can be collected within 24 hours. Ten years ago, just creating these images could have taken weeks or even months.
With an understanding of the structure of the coronavirus spike protein, and an ability to quickly serialize the testing of antibodies, researchers are hopeful to develop a vaccine that can be ready for clinical trials.
The National Institutes of Health Director’s blog discussed the impact of cryo-EM on the SARS-CoV-2 spike protein research and outlined the next steps to develop vaccine candidates.
Leah Lavery, PhD is a Product Marketing Manager at Thermo Fisher Scientific.
Speak with an expert: https://www.thermofisher.com/blog/microscopy/speak-with-an-expert/
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