9C7Z

Hallucinated C3 protein assembly HALC3_919

9C7Z の概要

• エントリーDOI: 10.2210/pdb9c7z/pdb
• 分子名称: HALC3_919, TETRAETHYLENE GLYCOL (3 entities in total)
• 機能のキーワード: trimer, hallucination, de novo, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16350.76

構造登録者

Ragotte, R.,Bera, A.,Milles, L.F.,Wicky, B.I.M.,Baker, D. (登録日: 2024-06-11, 公開日: 2025-05-21, 最終更新日: 2025-12-10)

主引用文献

Ragotte, R.J.,Tortorici, M.A.,Catanzaro, N.J.,Addetia, A.,Coventry, B.,Froggatt, H.M.,Lee, J.,Stewart, C.,Brown, J.T.,Goreshnik, I.,Sims, J.N.,Milles, L.F.,Wicky, B.I.M.,Glogl, M.,Gerben, S.,Kang, A.,Bera, A.K.,Sharkey, W.,Schafer, A.,Harkema, J.R.,Baric, R.S.,Baker, D.,Veesler, D.
Designed miniproteins potently inhibit and protect against MERS-CoV.
Cell Rep, 44:115760-115760, 2025

PubMed Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen with a 36% case-fatality rate in humans. No vaccines or specific therapeutics are currently approved for use in humans or the camel host reservoir. Here, we computationally designed monomeric and homo-oligomeric miniproteins that bind with high affinity to the MERS-CoV spike (S) glycoprotein, the main target of neutralizing antibodies and vaccine development. We show that these miniproteins broadly neutralize a panel of MERS-CoV S variants, spanning the known antigenic diversity of this pathogen, by targeting a conserved site in the receptor-binding domain (RBD). The miniproteins directly compete with binding of the dipeptidylpeptidase 4 (DPP4) receptor to MERS-CoV S, thereby blocking viral attachment to the host entry receptor and subsequent membrane fusion. Intranasal administration of a lead miniprotein provides prophylactic protection against stringent MERS-CoV challenge in mice, motivating its future clinical development as a next-generation countermeasure against this virus with pandemic potential.

PubMed: 40450691
DOI: 10.1016/j.celrep.2025.115760

実験手法

X-RAY DIFFRACTION (2.1 Å)