Publication date: Jan 24, 2025
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.
| Concepts | Keywords |
|---|---|
| Angiotensin | coronavirus |
| Antiviral | dual-functional antivirals |
| Captured | membrane fusion mechanism |
| Coronaviruses | spike |
| Enzyme |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | viral infection |
| disease | IDO | protein |
| disease | MESH | infection |
| disease | MESH | coronavirus infection |