8Z4X

Cryo-EM structure of SARS-CoV-2 D614G S with two ACE2 receptors binding (RB2) in prefusion conformation

Summary for 8Z4X

• Entry DOI: 10.2210/pdb8z4x/pdb
• EMDB information: 39771
• Descriptor: Spike glycoprotein, Angiotensin-converting enzyme 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: spike-ace2 complex, viral protein/hydrolase, viral protein-hydrolase complex
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 5
• Total formula weight: 591014.39

Authors

Liu, Z.,Xing, L. (deposition date: 2024-04-17, release date: 2025-02-05, Last modification date: 2025-07-23)

Primary citation

Xing, L.,Liu, Z.,Wang, X.,Liu, Q.,Xu, W.,Mao, Q.,Zhang, X.,Hao, A.,Xia, S.,Liu, Z.,Sun, L.,Zhang, G.,Wang, Q.,Chen, Z.,Jiang, S.,Sun, L.,Lu, L.
Early fusion intermediate of ACE2-using coronavirus spike acting as an antiviral target.
Cell, 188:1297-1314.e24, 2025

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 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.

PubMed: 39889696
DOI: 10.1016/j.cell.2025.01.012

Experimental method

ELECTRON MICROSCOPY (3.4 Å)