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Liu, Juan; Mao, Fengfeng; Chen, Jianhe; Lu, Shuaiyao; Qi, Yonghe; Sun, Yinyan; Fang, Linqiang; Yeung, Man Lung; Liu, Chunmei; Yu, Guimei; Li, Guangyu; Liu, Ximing; Yao, Yuansheng; Huang, Panpan; Hao, Dongxia; Liu, Zibing; Ding, Yu; Liu, Haimo; Yang, Fang; Chen, Pan; Sa, Rigai; Sheng, Yao; Tian, Xinxin; Peng, Ran; Li, Xue; Luo, Junmian; Cheng, Yurui; Zheng, Yule; Lin, Yongqing; Song, Rui; Jin, Ronghua; Huang, Baoying; Choe, Hyeryun; Farzan, Michael; Yuen, Kwok-Yung; Tan, Wenjie; Peng, Xiaozhong; Sui, Jianhua; Li, Wenhui
Nature communications, 08/2023, Letnik: 14, Številka: 1Journal Article
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.
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in: SICRIS
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