7Y9N

an engineered 5-helix bundle derived from SARS-CoV-2 S2 in complex with HR2P

Summary for 7Y9N

• Entry DOI: 10.2210/pdb7y9n/pdb
• Descriptor: Spike protein S2',5HB-H2, SARS-coV-2 S2 subunit (3 entities in total)
• Functional Keywords: 5hb, virus protein/inhibitor, virus protein-inhibitor complex
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 2
• Total formula weight: 30361.70

Authors

Lu, G.W.,Lin, X.,Guo, L.Y.,Lin, S. (deposition date: 2022-06-25, release date: 2022-08-17, Last modification date: 2023-11-29)

Primary citation

Lin, X.,Guo, L.,Lin, S.,Chen, Z.,Yang, F.,Yang, J.,Wang, L.,Wen, A.,Duan, Y.,Zhang, X.,Dai, Y.,Yin, K.,Yuan, X.,Yu, C.,He, B.,Cao, Y.,Dong, H.,Li, J.,Zhao, Q.,Lu, G.
An engineered 5-helix bundle derived from SARS-CoV-2 S2 pre-binds sarbecoviral spike at both serological- and endosomal-pH to inhibit virus entry.
Emerg Microbes Infect, 11:1920-1935, 2022

PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related sarbecoviruses enter host cells by receptor-recognition and membrane-fusion. An indispensable step in fusion is the formation of 6-helix bundle by viral spike heptad repeats 1 and 2 (HR1 and HR2). Here, we report the construction of 5-helix bundle (5HB) proteins for virus infection inhibition. The optimal construct inhibits SARS-CoV-2 pseudovirus entry with sub-micromolar IC50. Unlike HR2-based peptides that cannot bind spike in the pre-fusion conformation, 5HB features with the capability of binding to pre-fusion spike. Furthermore, 5HB binds viral HR2 at both serological- and endosomal-pH, highlighting its entry-inhibition capacity when SARS-CoV-2 enters via either cell membrane fusion or endosomal route. Finally, we show that 5HB could neutralize S-mediated entry of the predominant SARS-CoV-2 variants and a wide spectrum of sarbecoviruses. These data provide proof-of-concept evidence that 5HB might be developed for the prevention and treatment of SARS-CoV-2 and other emerging sarbecovirus infections.

PubMed: 35757908
DOI: 10.1080/22221751.2022.2095308

Experimental method

X-RAY DIFFRACTION (1.885 Å)