7TZ0

Cryo-EM structure of SARS-CoV-2 spike in complex with FSR22, an anti-SARS-CoV-2 DARPin (Local refinement of FSR22 and RBD)

7TZ0 の概要

• エントリーDOI: 10.2210/pdb7tz0/pdb
• EMDBエントリー: 26201
• 分子名称: Spike glycoprotein, DARPin FSR22 (2 entities in total)
• 機能のキーワード: darpins, anti-sars-cov-2, therapeutics, covid-19, viral protein-antiviral protein complex, viral protein/antiviral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 162072.41

構造登録者

Kwon, Y.D.,Gorman, J.,Kwong, P.D. (登録日: 2022-02-15, 公開日: 2022-12-07, 最終更新日: 2024-10-09)

主引用文献

Chonira, V.,Kwon, Y.D.,Gorman, J.,Case, J.B.,Ku, Z.,Simeon, R.,Casner, R.G.,Harris, D.R.,Olia, A.S.,Stephens, T.,Shapiro, L.,Bender, M.F.,Boyd, H.,Teng, I.T.,Tsybovsky, Y.,Krammer, F.,Zhang, N.,Diamond, M.S.,Kwong, P.D.,An, Z.,Chen, Z.
A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins.
Nat.Chem.Biol., 19:284-291, 2023

PubMed Abstract: We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses, with respective IC values of 3.4, 2.2 and 7.4 ng ml for FSR16m. Cryo-EM structures revealed that these DARPins recognize a region of the receptor-binding domain (residues 456, 475, 486, 487 and 489) overlapping a critical portion of the angiotensin-converting enzyme 2 (ACE2)-binding surface. K18-hACE2 transgenic mice inoculated with B.1.617.2 and receiving intranasally administered FSR16m showed less weight loss and 10-100-fold lower viral burden in upper and lower respiratory tracts. The strong and broad neutralization potency makes FSR16m and FSR22 promising candidates for the prevention and treatment of infection by SARS-CoV-2.

PubMed: 36411391
DOI: 10.1038/s41589-022-01193-2

実験手法

ELECTRON MICROSCOPY (4.17 Å)