Cryo-EM in Coronavirus Research

An overview of coronavirus and COVID-19 research using electron microscopy and cryo-EM.

In the early days of cryo-EM, a great deal of research focused on solving the 3D structure of viruses. Today it continues to be a valuable technique for structural biologists, whose work contributes to the rapid pace of research on coronaviruses.

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Published Research

A round-up of published coronavirus research and articles involving Gatan’s technology and cryo-EM:

SARS-CoV-2 Nsp1 binds the ribosomal mRMA channel to inhibit translation
Nature Structural & Molecular Biology – September 9, 2020

Molecular architecture of the SARS-CoV-2 virus
Cell – September 3, 2020

In-situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges
bioRxiv – June 26, 2020
Solved with the BioQuantum K3 System

Distinct conformational states of SARS-CoV-2 spike protein
Science – July 21, 2020
Solved with the BioQuantum™ K3 System

  • Gatan cryo-EM technology was used to solve the structures of the COVID-19 spike protein in prefusion and postfusion conformations.
  • This provides insights into how the virus evades the immune system and enters cells.
  • The structures of spike protein conformational states are useful in vaccine strategy development.
Coronavirus prefusion and postfusion conformations

Structures, conformations, and distributions of SARS-CoV-2 spike protein trimers on intact virions
bioRxiv – June 27, 2020

  • The spike protein of the COVID-19 virus is highly flexible.
  • The conformational flexibility of spike protein protects the virus from the immune system and enables it to enter human cells.
  • Structures obtained from expressed and purified spike protein may provide information about its flexibility.
  • Cryo-EM structures of spike protein conformational states were obtained from intact frozen viruses and solved with Gatan instruments. These provide valuable information for vaccine development.

Potent neutralising monoclonal antibodies directed to multiple epitopes on the SARS-CoV-2 spike
bioRxiv – June 17, 2020
Solved with the K3 Direct Detection Camera

  • Virus-neutralising antibodies are one of the approaches to treat or prevent infection. These antibodies target the COVID-19 spike protein.
  • Researchers are using Gatan technology to examine how the virus-neutralising antibodies bind to the spike protein.
  • Cryo-EM structures enable virus-neutralising antibodies to be optimised as potential therapeutic agents against the virus.

Cross-neutralisation of SARS-CoV-2 by a human monoclonal SARS-CoV antibody
Nature – May 18, 2020

  • Antibodies are the body’s way of neutralising disease agents.
  • Vaccines teach the body how to make antibodies.
  • Antibodies can also be purified and used as a drug.
  • The cryo-EM structure of coronavirus obtained using Gatan’s instruments is useful in the design and optimisation of both vaccines and antibodies.
Coronavirus structure

Structure of the RNA-dependent RNA polymerase from COVID-19 virus
Science – May 15, 2020

  • Preliminary results show remdesivir reduces the recovery time for COVID-19 patients.
  • A structure was solved by cryo-EM using Gatan instruments, showing how remdesivir blocks virus replication.
  • Remdesivir can be further improved to target COVID-19 more effectively, using structure-based drug design techniques.
Remdesivir

Structure of the RNA-dependent RNA polymerase from COVID-19 virus
Science – April 10, 2020

  • The spike protein is the key target for vaccine and drug development efforts.
  • A patent was filed for a vaccine based on this structure, and the vaccine has promising results in clinical trials.
[testimonial author=”Lead Scientist, UT Austin”]The K3 camera not only gave us great images…, it also prevented data collection from becoming a bottleneck, ultimately letting our team concentrate on getting the structure as quickly as possible[/testimonial]

What the structure of the coronavirus can tell us
Washington Post article – March 23, 2020

Understanding the coronavirus structure is an important step to finding vaccines and treatments, through these steps:

  1. Identify the target structure, mechanism and dynamics involved in the disease.
  2. Precisely model an inhibitor (vaccine or therapeutic) and improve its effectiveness against the disease.
  3. Account for mutations that “drift” or “shift” a therapeutics’ efficacy over time.
  4. Reduce side effects.
Coronavirus (COVID-19)

Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2
Science – March 27, 2020
Solved with the K3 Direct Detection Camera

  • COVID-19 is pulled into cells after binding to a receptor on the surface.
  • Understanding how it binds, at atomic scale, enables drugs to be designed that block this from happening.
  • The K3 camera helped solve the coronavirus structure in record time.

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Science – March 13, 2020
Prepared with the Solarus Plasma Cleaner and solved with the K3 Direct Detection Camera
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Cryo-EM Instrumentation

Gatan BioContinuum

BioContinuum

Imaging filter for cyro-EM and cryo-ET

  • Combines the optics of the Gatan Continuum with the K3 electron-counting, direct detection camera.
  • Low dose imaging for beam-sensitive materials.
  • Large 24 megapixel field of view.

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Gatan K3 Camera

K3 Camera

Direct detection camera

  • Top of the range for imaging performance.
  • 1500 frames per second.
  • Electron counting for high image quality.
  • Low dose for beam-sensitive materials.

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Gatan Else

Elsa Cryo-Holder

Transfer cryo-EM samples frost-free

  • Perform longer, more ocmplex cryo experiments.
  • Reduced drift for better image quality.
  • Image radiation-sensitive, frozen-hydrated specimens.

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Gatan Latitude S Software

Latitude S

Cryo-EM data collection software

  • Designed for low-dose, single particle cryo-EM datasets.
  • Fully integrates your cryo-EM instrumentation, TEM column and camera.
  • Automated acquisition and quick screening.

More details…


More Information

Blue Scientific is the official distributor of Gatan’s complete range of systems for TEM and SEM in the Nordic region. We’re available to answer all your questions – just get in touch:

 Contact us on +44 (0)1223 422 269 or info@blue-scientific.com

 More about cryo-EM

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