COVID Research

Much of the early work in cryo-EM was focused on solving the 3D structure of important viruses. With the new coronavirus structure in the headlines, we thought it would be helpful to point out a number of the structural biologists whose work has contributed to the rapid pace of research on coronaviruses.

We would like to congratulate all the researchers for their tremendous efforts. The Gatan team takes great pride in the instrumentation that helps to accelerate this research.

In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges
Solved with the BioQuantum K3 System
Science - October 9, 2020

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

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

  • Cryo-EM structures of the COVID-19 spike protein in prefusion and postfusion conformations solved with Gatan equipment
  • Distinct conformational states of spike protein help scientists understand how the COVID-19 virus evades the immune system and enters human cells   
  • The structures of spike protein conformational states allow the development of vaccine strategies

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 a highly flexible protein.
  • The conformational flexibility of spike protein protects the COVID-19 virus from the immune system and allows viral entry in human cells
  • Structures obtained from expressed and purified spike protein might provide limited information on its flexibility  
  • Cryo-EM structures of spike protein conformational states obtained from intact frozen viruses and solved with Gatan equipment provides valuable information for vaccine development

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

  • Virus-neutralizing antibodies are one of the approaches to treat or prevent infection by the COVID-19 virus
  • The COVID-19 spike protein is the key target of virus-neutralizing antibodies
  • Scientist are using Gatan equipment to study the binding of virus-neutralizing antibodies to the COVID-19 spike protein
  • Cryo-EM structures allow optimization of virus-neutralizing antibodies as potential therapeutic agents against the COVID-19 virus 

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

  • Antibodies are the bodies way to neutralize disease agents
  • Vaccines are designed to teach the body how to make antibodies
  • Antibodies can be purified and used as a drug
  • Cryo-EM structure from Gatan equipment allows the design and optimization of both vaccines and antibodies

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

  • Preliminary results show remdesivir reduces recovery time for patients who receive the drug
  • A structure, solved by cryo-EM using Gatan equipment,  shows how remdesivir blocks virus replication
  • Remdesivir can be improved/optimized to better target COVID-19 using structure-based drug design

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
  • Patent was filed for a vaccine based on this structure
  • US Patent US20200061185A1 / US2017/058370 Pending
  • Vaccine in Clinical Trials with encouraging results      https://clinicaltrials.gov/ct2/show/NCT04283461
  • "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”  - UT Austin Lead Scientist

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

Understanding the coronavirus structure is important to build an effective vaccine or therapeutic.

  • Identify the target structure, mechanism, and dynamics involved in the disease
  • Precisely model an inhibitor (vaccine or therapeutic) and improve the effectiveness against the disease
  • Account for mutations that “drift” or “shift” a therapeutics' efficacy over time
  • Reduce side effects

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

  • COVID-19 is pulled into cells after binding to a surface receptor
  • Understanding how it binds, at an atomic resolution, allows us to design drugs to block this from happening
  • K3 Camera helped this team solve this structure in record time

 

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation 
Prepared with the Solarus® Plasma Cleaner and solved with the K3 Direct Detection Camera
Press release – February 19, 2020

 

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