An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants
Abstract Many 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-...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40933-3 |
| _version_ | 1797558389596749824 |
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| author | Juan Liu Fengfeng Mao Jianhe Chen Shuaiyao Lu Yonghe Qi Yinyan Sun Linqiang Fang Man Lung Yeung Chunmei Liu Guimei Yu Guangyu Li Ximing Liu Yuansheng Yao Panpan Huang Dongxia Hao Zibing Liu Yu Ding Haimo Liu Fang Yang Pan Chen Rigai Sa Yao Sheng Xinxin Tian Ran Peng Xue Li Junmian Luo Yurui Cheng Yule Zheng Yongqing Lin Rui Song Ronghua Jin Baoying Huang Hyeryun Choe Michael Farzan Kwok-Yung Yuen Wenjie Tan Xiaozhong Peng Jianhua Sui Wenhui Li |
| author_facet | Juan Liu Fengfeng Mao Jianhe Chen Shuaiyao Lu Yonghe Qi Yinyan Sun Linqiang Fang Man Lung Yeung Chunmei Liu Guimei Yu Guangyu Li Ximing Liu Yuansheng Yao Panpan Huang Dongxia Hao Zibing Liu Yu Ding Haimo Liu Fang Yang Pan Chen Rigai Sa Yao Sheng Xinxin Tian Ran Peng Xue Li Junmian Luo Yurui Cheng Yule Zheng Yongqing Lin Rui Song Ronghua Jin Baoying Huang Hyeryun Choe Michael Farzan Kwok-Yung Yuen Wenjie Tan Xiaozhong Peng Jianhua Sui Wenhui Li |
| author_sort | Juan Liu |
| collection | DOAJ |
| description | Abstract Many 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 high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was developed as an inhaled formulation that achieves appropriate aerodynamic properties for rodent and monkey respiratory system delivery, and we found that early administration of HH-120 by aerosol inhalation significantly reduced viral loads and lung pathology scores in male golden Syrian hamsters infected by the SARS-CoV-2 ancestral strain (GDPCC-nCoV27) and the Delta variant. Our study presents a meaningful advancement in the inhalation delivery of large biologics like HH-120 (molecular weight (MW) ~ 1000 kDa) and demonstrates that HH-120 can serve as an efficacious, safe, and convenient agent against SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 has the potential to be efficacious against additional emergent coronaviruses. |
| first_indexed | 2024-03-10T17:30:47Z |
| format | Article |
| id | doaj.art-8b118b6b063b457f8f4c4940e76438c7 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:30:47Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-8b118b6b063b457f8f4c4940e76438c72023-11-20T10:02:11ZengNature PortfolioNature Communications2041-17232023-08-0114111810.1038/s41467-023-40933-3An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variantsJuan Liu0Fengfeng Mao1Jianhe Chen2Shuaiyao Lu3Yonghe Qi4Yinyan Sun5Linqiang Fang6Man Lung Yeung7Chunmei Liu8Guimei Yu9Guangyu Li10Ximing Liu11Yuansheng Yao12Panpan Huang13Dongxia Hao14Zibing Liu15Yu Ding16Haimo Liu17Fang Yang18Pan Chen19Rigai Sa20Yao Sheng21Xinxin Tian22Ran Peng23Xue Li24Junmian Luo25Yurui Cheng26Yule Zheng27Yongqing Lin28Rui Song29Ronghua Jin30Baoying Huang31Hyeryun Choe32Michael Farzan33Kwok-Yung Yuen34Wenjie Tan35Xiaozhong Peng36Jianhua Sui37Wenhui Li38National Institute of Biological SciencesHuahui Health LtdHuahui Health LtdNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeHuahui Health LtdNational Institute of Biological SciencesNational Institute of Biological SciencesDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongHuahui Health LtdHuahui Health LtdHuahui Health LtdNational Institute of Biological SciencesHuahui Health LtdHuahui Health LtdHuahui Health LtdHuahui Health LtdHuahui Health LtdHuahui Health LtdHuahui Health LtdHuahui Health LtdHuahui Health LtdNational Institute of Biological SciencesNational Institute of Biological SciencesHuahui Health LtdHuahui Health LtdHuahui Health LtdHuahui Health LtdHuahui Health LtdHuahui Health LtdBeijing Ditan Hospital, Capital Medical UniversityBeijing Ditan Hospital, Capital Medical UniversityNational Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC)Department of Immunology and Microbiology, Scripps ResearchDepartment of Immunology and Microbiology, Scripps ResearchDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongNational Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC)National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Institute of Biological SciencesNational Institute of Biological SciencesAbstract Many 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 high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern. HH-120 was developed as an inhaled formulation that achieves appropriate aerodynamic properties for rodent and monkey respiratory system delivery, and we found that early administration of HH-120 by aerosol inhalation significantly reduced viral loads and lung pathology scores in male golden Syrian hamsters infected by the SARS-CoV-2 ancestral strain (GDPCC-nCoV27) and the Delta variant. Our study presents a meaningful advancement in the inhalation delivery of large biologics like HH-120 (molecular weight (MW) ~ 1000 kDa) and demonstrates that HH-120 can serve as an efficacious, safe, and convenient agent against SARS-CoV-2 variants. Finally, given the known role of ACE2 in viral reception, it is conceivable that HH-120 has the potential to be efficacious against additional emergent coronaviruses.https://doi.org/10.1038/s41467-023-40933-3 |
| spellingShingle | Juan Liu Fengfeng Mao Jianhe Chen Shuaiyao Lu Yonghe Qi Yinyan Sun Linqiang Fang Man Lung Yeung Chunmei Liu Guimei Yu Guangyu Li Ximing Liu Yuansheng Yao Panpan Huang Dongxia Hao Zibing Liu Yu Ding Haimo Liu Fang Yang Pan Chen Rigai Sa Yao Sheng Xinxin Tian Ran Peng Xue Li Junmian Luo Yurui Cheng Yule Zheng Yongqing Lin Rui Song Ronghua Jin Baoying Huang Hyeryun Choe Michael Farzan Kwok-Yung Yuen Wenjie Tan Xiaozhong Peng Jianhua Sui Wenhui Li An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants Nature Communications |
| title | An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants |
| title_full | An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants |
| title_fullStr | An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants |
| title_full_unstemmed | An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants |
| title_short | An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants |
| title_sort | igm like inhalable ace2 fusion protein broadly neutralizes sars cov 2 variants |
| url | https://doi.org/10.1038/s41467-023-40933-3 |
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