Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection.

2024-12

Bu, Fan

Ye, Gang

Morsheimer, Kimberly

Mendoza, Alise

Turner-Hubbard, Hailey

Herbst, Morgan

Spiller, Benjamin

Wadzinski, Brian E

Eaton, Brett

Anantpadma, Manu

Yang, Ge

Liu, Bin

Davey, Robert

Li, Fang

Journal Article

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0000-0002-1958-366X

10.1371/journal.ppat.1012817

The Ebola filovirus (EBOV) poses a serious threat to global health and national security. Nanobodies, a type of single-domain antibody, have demonstrated promising therapeutic potential. We identified two anti-EBOV nanobodies, Nanosota-EB1 and Nanosota-EB2, which specifically target the EBOV glycoprotein (GP). Cryo-EM and biochemical data revealed that Nanosota-EB1 binds to the glycan cap of GP1, preventing its protease cleavage, while Nanosota-EB2 binds to critical membrane-fusion elements in GP2, stabilizing it in the pre-fusion state. Nanosota-EB2 is a potent neutralizer of EBOV infection in vitro and offers excellent protection in a mouse model of EBOV challenge, while Nanosota-EB1 provides moderate neutralization and protection. Nanosota-EB1 and Nanosota-EB2 are the first nanobodies shown to inhibit authentic EBOV. Combined with our newly developed structure-guided in vitro evolution approach, they lay the foundation for nanobody-based therapies against EBOV and other viruses within the ebolavirus genus.

link

PLoS pathogens 2024-12; 20(12)

PLoS pathogens

1553-7374