An IgM-like Inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2-Reference-Cited by-同舟云学术

An IgM-like Inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2

Published:2022-10-31 Issue: Volume: Page:
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Author:

Li Wenhui¹^ORCID,Liu Juan²,Mao Fengfeng²,Chen Jianhe²,Lu Shuaiyao³^ORCID,Qi Yonghe²,Sun Yinyan¹,Fang Linqiang⁴,Yeung Man Lung⁵,Liu Chunmei²,Yu Guimei²,Li Guangyu²,Liu Ximing⁴^ORCID,Yao Yuansheng²,Huang Panpan²,Hao Dongxia²,Liu Zibing²,Ding Yu²,Liu Haimo²,Yang Fang²,Chen Pan²,Sa Rigai²,Sheng Yao⁴,Tian Xinxin¹^ORCID,Peng Ran²,Li Xue²,Luo Junmian²,Cheng Yurui²,Zheng Yule²,Lin Yongqing²,Song Rui⁶,Jin Ronghua⁶,Huang Baoying⁷,Choe Hyeryun⁸,Farzan Michael⁸,Yuen Kwok-Yung⁵^ORCID,Tan Wenjie⁹^ORCID,Peng Xiaozhong¹⁰^ORCID,Sui Jianhua¹¹^ORCID

Affiliation:

1. National Institute of Biological Sciences

2. Huahui Health Ltd.

3. National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan China and State Key Laborato

4. National Institute of Biological Sciences, Beijing

5. The University of Hong Kong

6. Beijing Ditan Hospital

7. Key Laboratory of Medical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC

8. Department of Immunology and Microbiology, Scripps Biomedical Research, University of Florida

9. China CDC

10. Institute of Medical Biology,Chinese Academy of Medical Sciences

11. Harvard Medical School

Abstract

AbstractMany of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)—the cellular receptor of SARS-CoV-2—into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with exceptionally high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was successfully developed as an inhaled formulation that achieves appropriate aerodynamic properties for respiratory system delivery, and we found that aerosol inhalation of HH-120 significantly reduced viral loads and lung pathology scores in golden Syrian hamsters infected by the SARS-CoV-2 wild-type strain and the Delta variant. Our study presents a breakthrough for the inhalation delivery of large biologics like HH-120 (molecular weight ~ 1000kDa) and demonstrates that HH-120 can serve as a highly efficacious, safe, and convenient agent against all SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 will be efficacious against additional emergent coronaviruses.

Publisher

Research Square Platform LLC

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