7WD2

Crystal structure of S43 bound to SARS-CoV-2 RBD

Summary for 7WD2

• Entry DOI: 10.2210/pdb7wd2/pdb
• Descriptor: Spike protein S1, Anti-RON nanobody, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: sars-cov-2, rbd, s43, complex, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 4
• Total formula weight: 74378.37

Authors

Wang, Q.H.,Gao, G.F.,Qi, J.X.,Su, C.,Liu, H.H.,Wu, L.L. (deposition date: 2021-12-20, release date: 2022-12-21, Last modification date: 2024-11-13)

Primary citation

Liu, H.,Wu, L.,Liu, B.,Xu, K.,Lei, W.,Deng, J.,Rong, X.,Du, P.,Wang, L.,Wang, D.,Zhang, X.,Su, C.,Bi, Y.,Chen, H.,Liu, W.J.,Qi, J.,Cui, Q.,Qi, S.,Fan, R.,Jiang, J.,Wu, G.,Gao, G.F.,Wang, Q.
Two pan-SARS-CoV-2 nanobodies and their multivalent derivatives effectively prevent Omicron infections in mice.
Cell Rep Med, 4:100918-100918, 2023

PubMed Abstract: With the widespread vaccinations against coronavirus disease 2019 (COVID-19), we are witnessing gradually waning neutralizing antibodies and increasing cases of breakthrough infections, necessitating the development of drugs aside from vaccines, particularly ones that can be administered outside of hospitals. Here, we present two cross-reactive nanobodies (R14 and S43) and their multivalent derivatives, including decameric ones (fused to the immunoglobulin M [IgM] Fc) that maintain potent neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after aerosolization and display not only pan-SARS-CoV-2 but also varied pan-sarbecovirus activities. Through respiratory administration to mice, monovalent and decameric R14 significantly reduce the lung viral RNAs at low dose and display potent pre- and post-exposure protection. Furthermore, structural studies reveal the neutralizing mechanisms of R14 and S43 and the multiple inhibition effects that the multivalent derivatives exert. Our work demonstrates promising convenient drug candidates via respiratory administration against SARS-CoV-2 infection, which can contribute to containing the COVID-19 pandemic.

PubMed: 36702124
DOI: 10.1016/j.xcrm.2023.100918

Experimental method

X-RAY DIFFRACTION (2.69 Å)