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| Title | Early fusion intermediate of ACE2-using coronavirus spike acting as an antiviral target. |
|---|---|
| Journal, issue, pages | Cell, Vol. 188, Issue 5, Page 1297-1314.e24, Year 2025 |
| Publish date | Mar 6, 2025 |
Authors | Lixiao Xing / Zhimin Liu / Xinling Wang / Qianying Liu / Wei Xu / Qiyu Mao / Xiang Zhang / Aihua Hao / Shuai Xia / Zezhong Liu / Lujia Sun / Guangxu Zhang / Qian Wang / Zhenguo Chen / Shibo Jiang / Lei Sun / Lu Lu / ![]() |
| PubMed Abstract | Coronavirus fusion with and entry into the host cell depends on viral spike, which acts as a crucial component of viral infection. However, the lack of receptor-activated spike intermediate ...Coronavirus fusion with and entry into the host cell depends on viral spike, which acts as a crucial component of viral infection. However, the lack of receptor-activated spike intermediate conformation has hindered a comprehensive understanding of spike-induced membrane fusion. Here, we captured an angiotensin-converting enzyme 2 (ACE2)-induced early fusion intermediate conformation (E-FIC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike in which heptad repeat 1 (HR1) in S2 has ejected while S1 remains attached. This E-FIC can transition to the late FIC after S2' cleavage. Leveraging this discovery, we designed an E-FIC-targeted dual-functional antiviral protein, AL5E. AL5E effectively inactivated ACE2-using coronaviruses and inhibited their infection, outperforming a mono-functional antiviral in protecting animals against these coronaviruses. This study has identified the E-FIC and used it as a target for the development of a dual-functional antiviral for the prevention and treatment of ACE2-using coronavirus infection. |
External links | Cell / PubMed:39889696 |
| Methods | EM (single particle) |
| Resolution | 2.99 - 3.92 Å |
| Structure data | EMDB-39756, PDB-8z3w: EMDB-39771, PDB-8z4x: EMDB-39791, PDB-8z64: EMDB-39796, PDB-8z6a: EMDB-39811, PDB-8z7b: EMDB-39813, PDB-8z7g: ![]() EMDB-39817: Cryo-EM structure of SARS-CoV-2 S trimer in the early fusion intermediate conformation (E-FIC) (focused refinement of S2-bottom) ![]() EMDB-39818: Cryo-EM structure of SARS-CoV-2 S trimer in the early fusion intermediate conformation (E-FIC) (focused refinement of S2-top) EMDB-39819, PDB-8z7l: EMDB-39822, PDB-8z7p: |
| Chemicals | ![]() ChemComp-NAG: |
| Source |
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Keywords | VIRAL PROTEIN/HYDROLASE / Spike-ACE2 complex / VIRAL PROTEIN-HYDROLASE complex / VIRAL PROTEIN / VIRAL PROTEIN/HTDROLASE / VIRAL PROTEIN-HTDROLASE complex |
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homo sapiens (human)
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