9DGO

Designed miniproteins potently inhibit and protect against MERS-CoV. Crystal structure of MERS-CoV S RBD in complex with miniprotein cb3

9DGO の概要

• エントリーDOI: 10.2210/pdb9dgo/pdb
• 関連するPDBエントリー: 9DKK
• 分子名称: Spike glycoprotein, Designed miniprotein cb_3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: mers-cov, miniproteins, neutralization, fusion, cryo-em, biolayer interferometry, mers-cov strains, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein
• 由来する生物種: Middle East respiratory syndrome-related coronavirus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 71620.58

構造登録者

Tortorici, M.A.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2024-09-03, 公開日: 2025-06-18)

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 (1.85 Å)