| HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor via intranasal administration |
| Lu, Y; Shen, F; He, WQ; Li, AQ; Li, MH; Feng, XL; Zheng, YT; Pang, W
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| 2023
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| 发表期刊 | ACTA PHARMACEUTICA SINICA B
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| ISSN | 2211-3835
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| 卷号 | 13期号:8页码:3339-3351 |
| 摘要 | The continuously emerging SARS-CoV-2 variants pose a great challenge to the efficacy of current drugs, this necessitates the development of broad-spectrum antiviral drugs. In the previous study, we designed a recombinant protein, heptad repeat (HR) 121, as a variant-proof vaccine. Here, we found it can act as a fusion inhibitor and demonstrated broadly neutralizing activities against SARS-CoV-2 and its main variants. Structure analysis suggested that HR121 targets the HR2 domain in SARS-CoV-2 spike (S) 2 subunit to block virus-cell fusion. Functional experiments demonstrated that HR121 can bind HR2 at serological-pH and endosomal-pH, highlighting its inhibition capacity when SARS-CoV-2 enters via either cellular membrane fusion or endosomal route. Importantly, HR121 can effectively inhibit SARS-CoV-2 and Omicron variant pseudoviruses entering the cells, as well as block authentic SARSCoV-2 and Omicron BA.2 replications in human pulmonary alveolar epithelial cells. After intranasal administration to Syrian golden hamsters, it can protect hamsters from SARS-CoV-2 and Omicron BA.2 infection. Together, our results suggest that HR121 is a potent drug candidate with broadly neutralizing activities against SARS-CoV-2 and its variants. 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| 收录类别 | SCI
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/13962
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| 专题 | 科研部门_分子免疫药理学（郑永唐）
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推荐引用方式
GB/T 7714 |
Lu, Y,Shen, F,He, WQ,et al. HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor via intranasal administration[J]. ACTA PHARMACEUTICA SINICA B,2023,13(8):3339-3351.
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| APA |
Lu, Y.,Shen, F.,He, WQ.,Li, AQ.,Li, MH.,...&Pang, W.(2023).HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor via intranasal administration.ACTA PHARMACEUTICA SINICA B,13(8),3339-3351.
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| MLA |
Lu, Y,et al."HR121 targeting HR2 domain in S2 subunit of spike protein can serve as a broad-spectrum SARS-CoV-2 inhibitor via intranasal administration".ACTA PHARMACEUTICA SINICA B 13.8(2023):3339-3351.
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