National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI089728
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI110700
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI171954
米国
引用
ジャーナル: PLoS Pathog / 年: 2024 タイトル: Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection. 著者: 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 / ...著者: 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 / 要旨: 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 ...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.