9IQP

Crystal structure of the Wuhan SARS-CoV-2 Spike RBD (319-541) complexed with 1p1B10 nanobody

Summary for 9IQP

• Entry DOI: 10.2210/pdb9iqp/pdb
• Descriptor: Spike protein S1, Nanobody 1p1B10, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: sars-cov-2, spike glycoprotein receptor-binding domain, complex with nanobody, antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 2
• Total formula weight: 43237.04

Authors

Sluchanko, N.N.,Matyuta, I.O.,Dronova, E.A.,Favorskaya, I.A.,Esmagambetov, I.B.,Shcheblyakov, D.V.,Logunov, D.Y.,Gintsburg, A.L.,Popov, V.O.,Boyko, K.M. (deposition date: 2024-07-13, release date: 2025-07-16)

Primary citation

Shcheblyakov, D.V.,Favorskaya, I.A.,Dolzhikova, I.V.,Korobkova, A.I.,Alekseeva, I.A.,Esmagambetov, I.B.,Voronina, O.L.,Tukhvatulin, A.I.,Zubkova, O.V.,Derkaev, A.A.,Ryabova, E.I.,Iliukhina, A.A.,Zorkov, I.D.,Grousova, D.M.,Reshetnikov, D.A.,Ryzhova, N.N.,Ermolova, E.I.,Kunda, M.S.,Matyuta, I.O.,Boyko, K.M.,Popov, V.O.,Logunov, D.Y.,Sluchanko, N.N.,Gintsburg, A.L.
Ultra-potent RBM-specific single-domain antibody broadly neutralizes multiple SARS-CoV-2 variants with picomolar activity.
Int.J.Biol.Macromol., 319:145386-145386, 2025

PubMed Abstract: SARS-CoV-2 infection remains a cause of severe illness in high-risk individuals, with few antiviral agents currently available. The emergence of new SARS-CoV-2 variants accumulating an increasing number of mutations significantly challenges the development of effective therapeutics. We describe broadly neutralizing single-domain antibody 1p1B10 having picomolar activity against both previously circulating SARS-CoV-2 variants, including Wuhan D614G, Alpha, Beta, Gamma, Delta and Omicron BA.1, BA.2, BA.5, and more recent variants - XBB.1, XBB.1.5, XBB.1.9, XBB.1.16, JN.1 and KS.1. We explained this broad activity by solving a high-resolution crystal structure of the S-protein RBD complex with the 1p1B10 antibody. The RBD/1p1B10 interface is unaffected by accumulated mutations and substantially overlaps with the RBD/ACE2 interface. 1p1B10 acts through binding to RBD both in open and closed conformations and blocking SARS-CoV-2 attachment to cells via direct competition with the ACE2 receptor. Therapeutic 1p1B10-Fc administration at a low dose of 1 mg/kg substantially reduced viral load in the lungs of Syrian hamsters after challenge with evolutionary distant SARS-CoV-2 variants and completely protected hACE2 mice against lethal SARS-CoV-2 infection. Overall, the findings make 1p1B10 a promising candidate for etiotropic treatment of COVID-19.

PubMed: 40543774
DOI: 10.1016/j.ijbiomac.2025.145386

Experimental method

X-RAY DIFFRACTION (1.55 Å)