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Related Concept Videos

Respiratory Syncytial Virus Disease01:29

Respiratory Syncytial Virus Disease

Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...
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Related Experiment Video

Updated: Jun 4, 2026

Engineering Antiviral Agents via Surface Plasmon Resonance
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Published on: June 14, 2022

Programmable antibody-based chimeric entry receptors for sarbecoviruses.

Yidan Wang1,2,3, Conrad En Zuo Chan4, Wilaiporn Saikruang5

  • 1Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.

Communications Biology
|June 2, 2026
PubMed
Summary

Researchers developed antibody-based chimeric entry receptors (ABCERs) to study sarbecoviruses. This new tool enables infection and replication of diverse viruses, including those independent of human ACE2 (hACE2), aiding in risk assessment and discovery.

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Area of Science:

  • Virology
  • Immunology
  • Biotechnology

Background:

  • Sarbecoviruses frequently spill over into animal populations, but most cannot infect humans due to their inability to engage human ACE2 (hACE2).
  • This limitation hinders mechanistic studies and risk assessment of zoonotic coronaviruses.
  • Existing methods struggle to study sarbecoviruses that do not utilize hACE2 for cell entry.

Purpose of the Study:

  • To develop a novel method for studying sarbecoviruses, particularly those independent of hACE2.
  • To create a programmable synthetic receptor platform for efficient viral entry and replication.
  • To assess the breadth of antibody recognition and evaluate vaccine-induced immunity against diverse sarbecoviruses.

Main Methods:

  • Engineered antibody-based chimeric entry receptors (ABCERs) by replacing the hACE2 extracellular domain with single-chain variable fragments (scFvs) from neutralizing antibodies.
  • Utilized scFvs to mimic viral engagement with the receptor, preserving essential intracellular fusion machinery.
  • Tested the ability of ABCERs to support infection and replication of various sarbecoviruses, including hACE2-independent strains.

Main Results:

  • ABCERs enabled efficient infection and replication of diverse sarbecoviruses from clinical and animal sources.
  • The E7 scFv demonstrated broad recognition of conserved epitopes across sarbecoviruses from all clades.
  • Vaccine-induced sera potently blocked E7 binding to SARS-CoV-2 but showed limited cross-inhibition against hACE2-independent sarbecoviruses, indicating an immunity gap.

Conclusions:

  • E7-based ABCERs provide a versatile synthetic receptor platform for studying sarbecoviruses beyond the hACE2-dependent pathway.
  • This platform facilitates the isolation, study, and surveillance of a broader range of zoonotic coronaviruses.
  • Findings highlight limitations in current vaccine-induced humoral immunity against diverse sarbecoviruses.