Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection.
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 glycopr...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-12-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012817 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841533262930903040 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Fan Bu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c1b4258e4a3e44debd43229941a36d96 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-c1b4258e4a3e44debd43229941a36d962025-01-17T05:31:04ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-12-012012e101281710.1371/journal.ppat.1012817Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection.Fan BuGang YeKimberly MorsheimerAlise MendozaHailey Turner-HubbardMorgan HerbstBenjamin SpillerBrian E WadzinskiBrett EatonManu AnantpadmaGe YangBin LiuRobert DaveyFang LiThe 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.https://doi.org/10.1371/journal.ppat.1012817 |
| spellingShingle | 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 Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection. PLoS Pathogens |
| title | Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection. |
| title_full | Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection. |
| title_fullStr | Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection. |
| title_full_unstemmed | Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection. |
| title_short | Discovery of Nanosota-EB1 and -EB2 as Novel Nanobody Inhibitors Against Ebola Virus Infection. |
| title_sort | discovery of nanosota eb1 and eb2 as novel nanobody inhibitors against ebola virus infection |
| url | https://doi.org/10.1371/journal.ppat.1012817 |
| work_keys_str_mv | AT fanbu discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT gangye discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT kimberlymorsheimer discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT alisemendoza discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT haileyturnerhubbard discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT morganherbst discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT benjaminspiller discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT brianewadzinski discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT bretteaton discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT manuanantpadma discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT geyang discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT binliu discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT robertdavey discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection AT fangli discoveryofnanosotaeb1andeb2asnovelnanobodyinhibitorsagainstebolavirusinfection |