OmniVira

Literature detail

Programmable antibody-based chimeric entry receptors for sarbecoviruses.

Yidan Wang1,2,3 Conrad En Zuo Chan4 Wilaiporn Saikruang5 Adrian Eng Zheng Kang1 Wan Ni Chia6 Kei Sato1,5,7,8,9,10,11,12,13 Feng Zhu1 Han Wang14 Beng Lee Lim1 Zi Wei Chia4 Barnaby Edward Young4 Haifeng Ye15 Lin-Fa Wang16,17 Chee Wah Tan18,19
Affiliations 19 institutions
  1. Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
  2. Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Synthetic Biology and Biomedical Engineering Laboratory, Biomedical Synthetic Biology Research Center, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, China.
  3. Chongqing Key Laboratory of Precision Optics, Chongqing Institute of East China Normal University, Chongqing, China.
  4. National Centre for Infectious Diseases, Singapore, Singapore.
  5. Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  6. Leyden Labs Asia, Singapore, Singapore.
  7. Department of Pathology, Immunology and Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  8. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
  9. International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  10. International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  11. Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan.
  12. MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
  13. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  14. Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.
  15. Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Synthetic Biology and Biomedical Engineering Laboratory, Biomedical Synthetic Biology Research Center, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, China. [email protected].
  16. Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore. [email protected].
  17. National Centre for Infectious Diseases, Singapore, Singapore. [email protected].
  18. Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore. [email protected].
  19. Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. [email protected].
PMID 42230999 2026 Commun Biol eng aheadofprint
PubMed DOI Browse context

Article

Publication summary

Despite frequent spillover of sarbecoviruses, most SARS-related viruses discovered in animals fail to engage human ACE2 (hACE2), limiting mechanistic insight and risk assessment. Here we developed antibody-based chimeric entry receptors (ABCERs) that reprogram antibody-antigen recognition into a synthetic, cell-anchored receptor interface. By replacing the extracellular protease domain of hACE2 with single-chain variable fragments (scFvs) from broadly neutralizing antibodies, ABCERs mimic viral receptor engagement while preserving the intracellular architecture required for cathepsin L-dependent endocytic fusion. This modular design converts antibody specificity into a programmable entry module, supporting efficient infection and replication of diverse sarbecoviruses from both clinical and animal sources. Among the tested scFvs, E7 exhibited exceptional breadth, recognizing conserved epitopes shared across representative sarbecoviruses from all clades. Sera from Pfizer-BioNTech mRNA-vaccinated individuals potently blocked E7 binding to SARS-CoV-2 but showed limited cross-inhibition of E7 interactions with RBDs from hACE2-independent sarbecoviruses, revealing a substantial gap in current vaccine-induced humoral immunity. Together, our findings establish E7-based ABCERs as a programmable synthetic receptor platform that bridges antibody recognition and viral propagation, offering a universal tool for isolating, studying, and surveying sarbecoviruses beyond the hACE2-dependent paradigm.

Structured evidence records

Evidence records

2 total
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.90
Key finding

Antibody-based chimeric receptors enabled efficient infection and replication of diverse sarbecoviruses from animal and clinical sources, demonstrating that receptor specificity can be reprogrammed beyond human ACE2 dependence.

Host
Not specified
Location
Not specified
Supporting text

ABCERs mimic viral receptor engagement ... supporting efficient infection and replication of diverse sarbecoviruses from both clinical and animal sources.

Method
synthetic receptor expression | infection assays | receptor binding analysis
Sample type
cell culture
Study design
in vitro experiment
Transmission direction
host-range experiment
Event type
synthetic receptor-mediated sarbecovirus infection assay
Genes or proteins
ACE2 | cathepsin L | spike protein | RBD
Receptors
human ACE2 | antibody-based chimeric entry receptors (ABCERs)
Mechanism types
receptor usage | entry compatibility
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.88
Key finding

The E7 antibody-derived chimeric receptor recognized conserved epitopes across sarbecoviruses from all clades, providing molecular evidence for cross-sarbecovirus binding breadth.

Host
Not specified
Location
Not specified
Supporting text

Among the tested scFvs, E7 exhibited exceptional breadth, recognizing conserved epitopes shared across representative sarbecoviruses from all clades.

Method
binding assays | chimeric receptor design
Study design
molecular engineering study
Transmission direction
molecular mechanism only
Event type
antibody-derived receptor binding breadth
Genes or proteins
E7 scFv | RBD | ACE2
Receptors
human ACE2 | E7-based ABCER
Mechanism types
broad receptor recognition | epitope conservation