tetano
Editor, Senior Moderator
Nat Commun
. 2023 Aug 25;14(1):5191.
doi: 10.1038/s41467-023-40933-3. An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants
Juan Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Fengfeng Mao[SUP] #[/SUP][SUP] 2 [/SUP], Jianhe Chen[SUP] #[/SUP][SUP] 2 [/SUP], Shuaiyao Lu[SUP] #[/SUP][SUP] 3 [/SUP], Yonghe Qi[SUP] #[/SUP][SUP] 2 [/SUP], Yinyan Sun[SUP] #[/SUP][SUP] 1 [/SUP], Linqiang Fang[SUP] 1 [/SUP], Man Lung Yeung[SUP] 4 5 6 7 8 [/SUP], Chunmei Liu[SUP] 2 [/SUP], Guimei Yu[SUP] 2 [/SUP], Guangyu Li[SUP] 2 [/SUP], Ximing Liu[SUP] 1 [/SUP], Yuansheng Yao[SUP] 2 [/SUP], Panpan Huang[SUP] 2 [/SUP], Dongxia Hao[SUP] 2 [/SUP], Zibing Liu[SUP] 2 [/SUP], Yu Ding[SUP] 2 [/SUP], Haimo Liu[SUP] 2 [/SUP], Fang Yang[SUP] 2 [/SUP], Pan Chen[SUP] 2 [/SUP], Rigai Sa[SUP] 2 [/SUP], Yao Sheng[SUP] 1 [/SUP], Xinxin Tian[SUP] 1 [/SUP], Ran Peng[SUP] 2 [/SUP], Xue Li[SUP] 2 [/SUP], Junmian Luo[SUP] 2 [/SUP], Yurui Cheng[SUP] 2 [/SUP], Yule Zheng[SUP] 2 [/SUP], Yongqing Lin[SUP] 2 [/SUP], Rui Song[SUP] 9 [/SUP], Ronghua Jin[SUP] 9 [/SUP], Baoying Huang[SUP] 10 [/SUP], Hyeryun Choe[SUP] 11 [/SUP], Michael Farzan[SUP] 11 [/SUP], Kwok-Yung Yuen[SUP] 4 5 6 7 8 [/SUP], Wenjie Tan[SUP] 10 [/SUP], Xiaozhong Peng[SUP] 12 13 [/SUP], Jianhua Sui[SUP] 14 15 [/SUP], Wenhui Li[SUP] 16 17 [/SUP]
Affiliations
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.
. 2023 Aug 25;14(1):5191.
doi: 10.1038/s41467-023-40933-3. An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants
Juan Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Fengfeng Mao[SUP] #[/SUP][SUP] 2 [/SUP], Jianhe Chen[SUP] #[/SUP][SUP] 2 [/SUP], Shuaiyao Lu[SUP] #[/SUP][SUP] 3 [/SUP], Yonghe Qi[SUP] #[/SUP][SUP] 2 [/SUP], Yinyan Sun[SUP] #[/SUP][SUP] 1 [/SUP], Linqiang Fang[SUP] 1 [/SUP], Man Lung Yeung[SUP] 4 5 6 7 8 [/SUP], Chunmei Liu[SUP] 2 [/SUP], Guimei Yu[SUP] 2 [/SUP], Guangyu Li[SUP] 2 [/SUP], Ximing Liu[SUP] 1 [/SUP], Yuansheng Yao[SUP] 2 [/SUP], Panpan Huang[SUP] 2 [/SUP], Dongxia Hao[SUP] 2 [/SUP], Zibing Liu[SUP] 2 [/SUP], Yu Ding[SUP] 2 [/SUP], Haimo Liu[SUP] 2 [/SUP], Fang Yang[SUP] 2 [/SUP], Pan Chen[SUP] 2 [/SUP], Rigai Sa[SUP] 2 [/SUP], Yao Sheng[SUP] 1 [/SUP], Xinxin Tian[SUP] 1 [/SUP], Ran Peng[SUP] 2 [/SUP], Xue Li[SUP] 2 [/SUP], Junmian Luo[SUP] 2 [/SUP], Yurui Cheng[SUP] 2 [/SUP], Yule Zheng[SUP] 2 [/SUP], Yongqing Lin[SUP] 2 [/SUP], Rui Song[SUP] 9 [/SUP], Ronghua Jin[SUP] 9 [/SUP], Baoying Huang[SUP] 10 [/SUP], Hyeryun Choe[SUP] 11 [/SUP], Michael Farzan[SUP] 11 [/SUP], Kwok-Yung Yuen[SUP] 4 5 6 7 8 [/SUP], Wenjie Tan[SUP] 10 [/SUP], Xiaozhong Peng[SUP] 12 13 [/SUP], Jianhua Sui[SUP] 14 15 [/SUP], Wenhui Li[SUP] 16 17 [/SUP]
Affiliations
- PMID: 37626079
- PMCID: PMC10457309
- DOI: 10.1038/s41467-023-40933-3
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.