7C02

Crystal structure of dimeric MERS-CoV receptor binding domain

Summary for 7C02

• Entry DOI: 10.2210/pdb7c02/pdb
• Descriptor: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: mers-cov, receptor binding domain, vaccine, virus, viral protein
• Biological source: Middle East respiratory syndrome-related coronavirus
• Total number of polymer chains: 2
• Total formula weight: 54450.10

Authors

Dai, L.,Qi, J.,Gao, G.F. (deposition date: 2020-04-30, release date: 2020-07-29, Last modification date: 2024-10-16)

Primary citation

Dai, L.,Zheng, T.,Xu, K.,Han, Y.,Xu, L.,Huang, E.,An, Y.,Cheng, Y.,Li, S.,Liu, M.,Yang, M.,Li, Y.,Cheng, H.,Yuan, Y.,Zhang, W.,Ke, C.,Wong, G.,Qi, J.,Qin, C.,Yan, J.,Gao, G.F.
A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS.
Cell, 182:722-, 2020

PubMed Abstract: Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.

PubMed: 32645327
DOI: 10.1016/j.cell.2020.06.035

Experimental method

X-RAY DIFFRACTION (2.91 Å)