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journal article·2025-11

Mechano‐Locking Strategy for Broad‐Spectrum SARS‐CoV‐2 Neutralization

Yang Ye, Shijie Chen, Yixiang Zhang, Tongtong Zhang, Tailin Liao, Zilin Ren, Wei Chen, Wei Hu

Small· Volume 21· Issue 47
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Source abstract

Abstract

Abstract Viral entry into host cells is typically initiated by interactions between viral surface proteins and host cell receptors. Conventional neutralization strategies aim to disrupt these interactions but often lose effectiveness against rapidly mutating viral strains. This challenge extends beyond SARS‐CoV‐2 to other viruses such as HIV and influenza. To overcome this limitation, a novel mechano‐locking strategy is proposed, using SARS‐CoV‐2 as a model system, in which bispecific antibodies (bsAbs) lock the spike protein in its prefusion conformation by preventing force‐induced conformational changes. These bsAbs demonstrate broad‐spectrum neutralization efficacy against multiple SARS‐CoV‐2 variants in pseudoviral assays. Single‐molecule magnetic tweezers experiments further reveal that these bsAbs significantly raise the mechanical force threshold required for S1–S2 dissociation, thereby enhancing spike protein mechano‐stability. This stabilization mechanism offers a mutation‐resistant approach to neutralization and introduces a new design paradigm for antiviral therapeutics. These findings establish a mechanistically driven framework for developing biomechanically enhanced strategies potentially applicable to a wide range of mechanically activated enveloped viruses.
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Research context

OpenAlex topics: SARS-CoV-2 and COVID-19 Research · Bacteriophages and microbial interactions · Monoclonal and Polyclonal Antibodies Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Kidney Disease Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Hangzhou Zhejiang 310058 China

Department of Cardiology of the Second Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Liangzhu Laboratory Zhejiang University Medical Center Hangzhou Zhejiang 310058 China

School of Information Science and Technology Northeast Normal University Changchun Jilin 130117 China

State Key Laboratory of Pathogen and Biosecurity Key Laboratory of Jilin Province for Zoonosis Prevention and Control Changchun Veterinary Research Institute Chinese Academy of Agricultural Sciences Changchun Jilin 130122 China

Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic Surgery Hangzhou First People's Hospital Hangzhou Zhejiang 310006 China

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Ministry of Education Frontier Science Center for Brain Science & Brain‐machine Integration State Key Laboratory for Modern Optical Instrumentation Key Laboratory for Biomedical Engineering of the Ministry of Education College of Biomedical Engineering and Instrument Science Zhejiang University Hangzhou Zhejiang 310012 China

Key Laboratory of Kidney Disease Prevention and Control Technology Zhejiang Clinical Research Center of Kidney and Urinary System Disease Institute of Nephrology Zhejiang University Hangzhou Zhejiang 310003 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Zhejiang Province

References (50)

Show source-provided references
1. 10.1038/s41580-021-00418-x10.1038/s41580-021-00418-x ↗
2. 10.1038/s41586-020-2012-710.1038/s41586-020-2012-7 ↗
3. 10.1016/j.tibs.2021.06.00110.1016/j.tibs.2021.06.001 ↗
4. 10.1016/j.cell.2024.09.02610.1016/j.cell.2024.09.026 ↗
5. 10.1016/j.cell.2020.05.02510.1016/j.cell.2020.05.025 ↗
6. 10.1016/j.cell.2021.05.00510.1016/j.cell.2021.05.005 ↗
7. 10.1038/s41586-020-2571-710.1038/s41586-020-2571-7 ↗
8. 10.1038/s41586-021-03807-610.1038/s41586-021-03807-6 ↗
9. 10.1016/j.cell.2022.12.01810.1016/j.cell.2022.12.018 ↗
10. 10.1016/j.cell.2023.12.02510.1016/j.cell.2023.12.025 ↗
11. 10.1016/j.cell.2021.12.04610.1016/j.cell.2021.12.046 ↗
12. 10.1016/j.cell.2022.01.01910.1016/j.cell.2022.01.019 ↗
13. 10.1038/s41586-022-05053-w10.1038/s41586-022-05053-w ↗
14. 10.1038/s41586-022-04594-410.1038/s41586-022-04594-4 ↗
15. 10.1038/s41586-022-04980-y10.1038/s41586-022-04980-y ↗
16. 10.1038/s41586-021-04388-010.1038/s41586-021-04388-0 ↗
17. 10.1073/pnas.211439711910.1073/pnas.2114397119 ↗
18. 10.1038/s41422-021-00558-x10.1038/s41422-021-00558-x ↗
19. 10.1016/j.xcrp.2022.10104810.1016/j.xcrp.2022.101048 ↗
20. 10.1038/s41565-023-01536-710.1038/s41565-023-01536-7 ↗
21. 10.1038/s41467-022-35641-310.1038/s41467-022-35641-3 ↗
22. 10.1126/science.abc695210.1126/science.abc6952 ↗
23. 10.1063/5.026703210.1063/5.0267032 ↗
24. 10.1126/science.abj332110.1126/science.abj3321 ↗
25. 10.1126/science.abq377310.1126/science.abq3773 ↗
26. 10.1016/j.chom.2022.10.01010.1016/j.chom.2022.10.010 ↗
27. 10.1126/scitranslmed.abi921510.1126/scitranslmed.abi9215 ↗
28. 10.1016/j.cell.2024.09.04310.1016/j.cell.2024.09.043 ↗
29. 10.1038/s41590-022-01138-w10.1038/s41590-022-01138-w ↗
30. 10.1038/s41467-022-33030-410.1038/s41467-022-33030-4 ↗
31. 10.1038/s41467-022-33284-y10.1038/s41467-022-33284-y ↗
32. 10.1126/scitranslmed.adq572010.1126/scitranslmed.adq5720 ↗
33. 10.1039/C8SC01319E10.1039/C8SC01319E ↗
34. 10.1038/s42004-019-0131-610.1038/s42004-019-0131-6 ↗
35. 10.1007/s41048-018-0064-010.1007/s41048-018-0064-0 ↗
36. 10.1038/sj.emboj.760126010.1038/sj.emboj.7601260 ↗
37. 10.1038/nature0339510.1038/nature03395 ↗
38. 10.1126/science.34757510.1126/science.347575 ↗
39. 10.1038/ncomms1196610.1038/ncomms11966 ↗
40. 10.1126/science.abb250710.1126/science.abb2507 ↗
41. 10.1038/s41467-023-38435-310.1038/s41467-023-38435-3 ↗
42. 10.1038/s41586-024-07487-w10.1038/s41586-024-07487-w ↗
43. 10.1002/prot.1038910.1002/prot.10389 ↗
44. 10.1016/j.celrep.2022.11034810.1016/j.celrep.2022.110348 ↗
45. 10.1016/j.chom.2021.12.01010.1016/j.chom.2021.12.010 ↗
46. 10.7554/eLife.0745410.7554/eLife.07454 ↗
47. 10.1093/bioinformatics/btw51410.1093/bioinformatics/btw514 ↗
48. 10.1016/j.softx.2015.06.00110.1016/j.softx.2015.06.001 ↗
49. 10.1002/jcc.2335410.1002/jcc.23354 ↗
50. 10.1063/1.44586910.1063/1.445869 ↗