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Related Concept Videos

Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

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The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
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Conjugated Proteins

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Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
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Antibody Actions01:26

Antibody Actions

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Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
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Viral Structure00:56

Viral Structure

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Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.
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Engineering Antiviral Agents via Surface Plasmon Resonance
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Structural basis for broad coronavirus neutralization.

Maximilian M Sauer1, M Alejandra Tortorici1,2, Young-Jun Park1

  • 1Department of Biochemistry, University of Washington, Seattle, WA, USA.

Nature Structural & Molecular Biology
|May 13, 2021
PubMed
Summary
This summary is machine-generated.

A novel antibody, B6, shows broad neutralizing activity against multiple beta-coronaviruses by targeting a conserved fusion epitope. This discovery offers a promising strategy for developing next-generation pan-coronavirus vaccines.

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Area of Science:

  • Virology and Immunology
  • Structural Biology
  • Vaccine Development

Background:

  • Three highly pathogenic beta-coronaviruses (SARS-CoV, MERS-CoV, SARS-CoV-2) have caused significant human epidemics.
  • The need for broad-spectrum antiviral therapies and vaccines against emerging coronaviruses is critical.
  • Identifying conserved targets for neutralizing antibodies is a key challenge in developing pan-coronavirus interventions.

Purpose of the Study:

  • To explore the potential of identifying monoclonal antibodies with broad neutralizing activity against beta-coronaviruses.
  • To characterize the structural basis of antibody cross-reactivity and neutralization mechanisms.
  • To provide a proof of concept for antibody-mediated broad coronavirus neutralization for vaccine design.

Main Methods:

  • Isolation and characterization of a monoclonal antibody (B6) with cross-reactivity against multiple beta-coronavirus spike glycoproteins.
  • Pseudotyped virus neutralization assays to assess the breadth of B6 activity across different coronavirus lineages.
  • Cryo-electron microscopy (Cryo-EM), X-ray crystallography, and membrane fusion assays to determine the binding site and mechanism of action.

Main Results:

  • The isolated antibody B6 demonstrated cross-reactivity with eight beta-coronavirus spike glycoproteins, including all five human-infecting types.
  • B6 broadly neutralized pseudotyped viruses from lineages A and C, but not lineage B (which includes SARS-CoV and SARS-CoV-2).
  • Structural analyses revealed that B6 binds to a conserved cryptic epitope within the viral fusion machinery, sterically hindering spike conformational changes necessary for membrane fusion.

Conclusions:

  • Antibody B6 provides a structural framework for understanding cross-reactivity against diverse beta-coronaviruses.
  • The findings demonstrate the feasibility of antibody-mediated broad coronavirus neutralization, applicable to vaccine strategies.
  • An unexpected target within the fusion machinery has been identified, paving the way for structure-guided design of next-generation pan-beta-coronavirus vaccines.