COVID Research

Cryo-EM has become an essential tool in fighting disease, and it has played a vital role in solving the 3D structure of the novel coronavirus. This structural insight has made possible the development and deployment of several vaccines to treat Covid 19. Numerous scientists have worked tirelessly to understand and combat this virus, and we wanted to highlight here the work that has contributed to the rapid, successful research on coronaviruses.

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

Cryo-EM research on COVID-19 accelerated with Gatan instrumentation. The cumulative number of SARS-CoV-2 cryo-EM research articles that utilized Gatan cameras rose to >80 within the first 10 months (left). Most of these articles were published in prestigious scientific journals with a broad readership (right). 

Native-like SARS-CoV-2 Spike Glycoprotein Expressed by ChAdOx1 nCoV-19/AZD1222 Vaccine
American Chemical Society - April 2, 2021

Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition
Cell Host & Microbe - January 13, 2021

Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape
Science - January 12, 2021

Mechanism of SARS-CoV-2 polymerase stalling by remdesivir
Nature Communications - January 12, 2021

Stabilizing the closed SARS-CoV-2 spike trimer
Nature Communications - January 11, 2021

Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections
Nature Communications - January 11, 2021

Cryo-EM structure of an extended SARS-CoV-2 replication and transcription complex reveals an intermediate state in cap synthesis
Cell - January 7, 2021

Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM
Science Advances - January 1, 2021

They spent 12 years solving a puzzle. It yielded the first COVID-19 vaccines.
National Geographic - December 31, 2020

Coronavirus infection induces progressive restructuring of the endoplasmic reticulum involving the formation and degradation of double membrane vesicles
Science Direct - December 24, 2020

Nonstructural protein 1 of SARS-CoV-2 is a potent pathogenicity factor redirecting host protein synthesis machinery toward viral RNA
Molecular Cell - December 17, 2020

Cryo-EM structures of SARS-CoV-2 spike without and with ACE2 reveal a pH-dependent switch to mediate endosomal positioning of receptor-binding domains
Solved with the Latitude S®  software and the BioQuantum™ K3® System
Science Direct - December 9, 2020

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2
Science - December 4, 2020

Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection
Cell Research - December 1, 2020

Structure-based development of human antibody cocktails against SARS-CoV-2
Cell Research - December 1, 2020

Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate
Science - November 27, 2020

Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms
Science - November 20, 2020

Architecture of a SARS-CoV-2 mini replication and transcription complex
Nature Communications - November 18, 2020

Structurally resolved SARS-CoV-2 antibody shows high efficacy in severely infected hamsters and provides a potent cocktail pairing strategy
Cell - November 12, 2020

Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology
Cell - November 12, 2020

Engineered trimeric ACE2 binds viral spike protein and locks it in “Three-up” conformation to potently inhibit SARS-CoV-2 infection
Cell Research - November 11, 2020

Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein
Science - November 6, 2020

An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive spike
Solved with the BioQuantum K3 System
Science - November 5, 2020

Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2
Nature Communications - November 4, 2020

The architecture of inactivated SARS-CoV-2 with postfusion spikes revealed by cryo-EM and cryo-ET
Structure - November 3, 2020

Structure-based design with tag-based purification and in-process biotinylation enable streamlined development of SARS-CoV-2 spike molecular probes
Cell Reports - October 27, 2020

De novo design of picomolar SARS-CoV-2 miniprotein inhibitors
Science - October 23, 2020

SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies
Nature - October 12, 2020

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

Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2
Cell Discovery - September 29, 2020

Structure-based design of prefusion-stabilized SARS-CoV-2 spikes
Science - September 18, 2020

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
Science - September 18, 2020

Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex
Cell - September 17, 2020

Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion
Nature - September 17, 2020

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

Neutralization of SARS-CoV-2 by destruction of the prefusion spike
Cell Host & Microbe - September 9, 2020

An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
Nature Communications - September 4, 2020

Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2
Science - September 4, 2020

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

Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail
Science - August 21, 2020

Structures of human antibodies bound to SARS-CoV-2 spike reveal common epitopes and recurrent features of antibodies
Cell - August 20, 2020

Structures, conformations, and distributions of SARS-CoV-2 spike protein trimers on intact virions
Nature - August 17, 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 into 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

SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography
bioRxiv - August 16, 2020

A neutralizing human antibody binds to the N-terminal domain of the spike protein of SARS-CoV-2
Science - August 7, 2020

Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient
Nature Structural & Molecular Biology - July 31, 2020

A thermostable, closed SARS-CoV-2 spike protein trimer
Nature Structural & Molecular Biology - July 31, 2020

Structural basis for RNA replication by the SARS-CoV-2 polymerase
Nature - July 23, 2020

Potent neutralizing monoclonal antibodies directed to multiple epitopes on the SARS-CoV-2 spike
Solved with the K3 Direct Detection Camera
Nature - July 22, 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 

 

Controlling the SARS-CoV-2 spike glycoprotein conformation
Nature Structural & Molecular Biology - July 22, 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

Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein
Nature Communications - July 17, 2020

Potently neutralizing and protective human antibodies against SARS-CoV-2
Nature - July 15, 2020

Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells
Cell - July 9, 2020

Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir
Science - June 26, 2020

Structural and biochemical characterization of the nsp12-nsp7-nsp8 core polymerase complex from SARS-CoV-2
Cell Reports - June 16, 2020

Structure of replicating SARS-CoV-2 polymerase
Nature - May 21, 2020

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 a structure-based drug design

Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein
Cell - April 16, 2020

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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