9P6X

Structure of EBOV glycoprotein in complex with Nanosota-EB1 and EB2

Summary for 9P6X

• Entry DOI: 10.2210/pdb9p6x/pdb
• EMDB information: 71328
• Descriptor: Envelope glycoprotein, Nanosota-EB1, Nanosota-EB2, ... (6 entities in total)
• Functional Keywords: ebov, glycoprotein, nanobody, viral protein
• Biological source: Ebola virus; More
• Total number of polymer chains: 9
• Total formula weight: 266873.85

Authors

Bu, F.,Ye, G.,Li, F. (deposition date: 2025-06-20, release date: 2026-01-21, Last modification date: 2026-04-29)

Primary citation

Bu, F.,Ye, G.,Morsheimer, K.,Turner-Hubbard, H.,Eaton, B.,Anantpadma, M.,Bheemanapally, K.,Tan, C.,Davey, R.,Li, F.
A highly potent and broadly accessible bispecific nanobody for the treatment of ebola virus infections.
Plos Pathog., 22:e1013878-e1013878, 2026

PubMed Abstract: Ebola virus (EBOV) causes recurring outbreaks, with a case fatality rate of about 40%. Currently approved vaccine and antibody therapies face major limitations, including only modest reductions in mortality and restricted accessibility due to their reliance on injection-based delivery and cold-chain transport and storage. To address these challenges, we developed a bispecific nanobody, Nanosota-EB1/EB2-Fc, composed of two nanobodies (camelid-derived single-domain antibodies, Nanosota-EB1 and Nanosota-EB2) that target distinct epitopes on the EBOV glycoprotein (GP) and are fused to a human Fc domain. Through cooperative contributions from both nanobodies, this bispecific nanobody strongly inhibits GP function and effectively overcomes the virus's decoy mechanism. A single dose provided strong protection in EBOV-infected mice, including when administered at late stages of infection. It was also effective when administered intranasally, offering a needle-free delivery option. Furthermore, its high in vitro stability indicates that it can be deployed without refrigeration. Taken together, this novel bispecific nanobody represents a promising next-generation therapeutic for EBOV, combining high potency with broad accessibility.

PubMed: 41592114
DOI: 10.1371/journal.ppat.1013878

Experimental method

ELECTRON MICROSCOPY (2.92 Å)