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

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2024 Dec 23

PMID 39715280

Authors

Fan Bu

Gang Ye

Kimberly Morsheimer

Alise Mendoza

Hailey Turner-Hubbard

Morgan Herbst

Benjamin Spiller

Brian E Wadzinski

Brett Eaton

Manu Anantpadma

Ge Yang

Bin Liu

Robert Davey

Fang Li

Affiliations

Soon will be listed here.

Abstract

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.

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