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Article: An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants

TitleAn IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants
Authors
Issue Date25-Aug-2023
PublisherNature Research
Citation
Nature Communications, 2023, v. 25, n. 14 How to Cite?
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.


Persistent Identifierhttp://hdl.handle.net/10722/339655
ISSN
2023 Impact Factor: 14.7
2023 SCImago Journal Rankings: 4.887
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, Juan-
dc.contributor.authorMao, Fengfeng-
dc.contributor.authorChen, Jianhe-
dc.contributor.authorLu, Shuaiyao-
dc.contributor.authorQi, Yonghe-
dc.contributor.authorSun, Yinyan-
dc.contributor.authorFang, Linqiang-
dc.contributor.authorYeung, Man Lung-
dc.contributor.authorLiu, Chunmei-
dc.contributor.authorYu, Guimei-
dc.contributor.authorLi, Guangyu-
dc.contributor.authorLiu, Ximing-
dc.contributor.authorYao, Yuansheng-
dc.contributor.authorHuang, Panpan-
dc.contributor.authorHao, Dongxia-
dc.contributor.authorLiu, Zibing-
dc.contributor.authorDing, Yu-
dc.contributor.authorLiu, Haimo-
dc.contributor.authorYang, Fang-
dc.contributor.authorChen, Pan-
dc.contributor.authorSa, Rigai-
dc.contributor.authorSheng, Yao-
dc.contributor.authorTian, Xinxin-
dc.contributor.authorPeng, Ran-
dc.contributor.authorLi, Xue-
dc.contributor.authorLuo, Junmian-
dc.contributor.authorCheng, Yurui-
dc.contributor.authorZheng, Yule-
dc.contributor.authorLin, Yongqing-
dc.contributor.authorSong, Rui-
dc.contributor.authorJin, Ronghua-
dc.contributor.authorHuang, Baoying-
dc.contributor.authorChoe, Hyeryun-
dc.contributor.authorFarzan, Michael-
dc.contributor.authorYuen, Kwok-Yung-
dc.contributor.authorTan, Wenjie-
dc.contributor.authorPeng, Xiaozhong-
dc.contributor.authorSui, Jianhua-
dc.contributor.authorLi, Wenhui-
dc.date.accessioned2024-03-11T10:38:18Z-
dc.date.available2024-03-11T10:38:18Z-
dc.date.issued2023-08-25-
dc.identifier.citationNature Communications, 2023, v. 25, n. 14-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/339655-
dc.description.abstract<p>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.<br></p>-
dc.languageeng-
dc.publisherNature Research-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleAn IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-023-40933-3-
dc.identifier.scopuseid_2-s2.0-85168727853-
dc.identifier.volume25-
dc.identifier.issue14-
dc.identifier.eissn2041-1723-
dc.identifier.isiWOS:001054831600003-
dc.identifier.issnl2041-1723-

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