7VOA

Crystal structure of SARS-CoV-2 RBD in complex with aRBD5

7VOA の概要

• エントリーDOI: 10.2210/pdb7voa/pdb
• 分子名称: alpaca nanobody, Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: viral protein-antiviral protein complex, viral protein/antiviral protein
• 由来する生物種: Vicugna pacos; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37205.51

構造登録者

Ma, H.,Zeng, W.H.,Jin, T.C. (登録日: 2021-10-13, 公開日: 2022-08-10, 最終更新日: 2024-11-13)

主引用文献

Ma, H.,Zhang, X.,Zheng, P.,Dube, P.H.,Zeng, W.,Chen, S.,Cheng, Q.,Yang, Y.,Wu, Y.,Zhou, J.,Hu, X.,Xiang, Y.,Zhang, H.,Chiu, S.,Jin, T.
Hetero-bivalent nanobodies provide broad-spectrum protection against SARS-CoV-2 variants of concern including Omicron.
Cell Res., 32:831-842, 2022

PubMed Abstract: SARS-CoV-2 variants with adaptive mutations have continued to emerge, causing fresh waves of infection even amongst vaccinated population. The development of broad-spectrum antivirals is thus urgently needed. We previously developed two hetero-bivalent nanobodies (Nbs), aRBD-2-5 and aRBD-2-7, with potent neutralization activity against the wild-type (WT) Wuhan isolated SARS-CoV-2, by fusing aRBD-2 with aRBD-5 and aRBD-7, respectively. Here, we resolved the crystal structures of these Nbs in complex with the receptor-binding domain (RBD) of the spike protein, and found that aRBD-2 contacts with highly-conserved RBD residues and retains binding to the RBD of the Alpha, Beta, Gamma, Delta, Delta plus, Kappa, Lambda, Omicron BA.1, and BA.2 variants. In contrast, aRBD-5 and aRBD-7 bind to less-conserved RBD epitopes non-overlapping with the epitope of aRBD-2, and do not show apparent binding to the RBD of some variants. However, when fused with aRBD-2, they effectively enhance the overall binding affinity. Consistently, aRBD-2-5-Fc and aRBD-2-7-Fc potently neutralized all of the tested authentic or pseudotyped viruses, including WT, Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.1.1 and BA.2. Furthermore, aRBD-2-5-Fc provided prophylactic protection against the WT and mouse-adapted SARS-CoV-2 in mice, and conferred protection against the Omicron BA.1 variant in hamsters prophylactically and therapeutically, indicating that aRBD-2-5-Fc could potentially benefit the prevention and treatment of COVID-19 caused by the emerging variants of concern. Our strategy provides new solutions in the development of broad-spectrum therapeutic antibodies for COVID-19.

PubMed: 35906408
DOI: 10.1038/s41422-022-00700-3

実験手法

X-RAY DIFFRACTION (1.8 Å)