Bibliographic Details
| Title: |
Rational Design of A Novel Small-Molecule HIV-1 Inactivator Targeting Both gp120 and gp41 of HIV-1 |
| Authors: |
Jing Pu, Yu Dai, Qian Wang, Lu Lu, Junqi Zhang, Wei Xu, Lan Xie, Shengqi Wang, Fei Yu, Xiaoyang He, Shibo Jiang |
| Source: |
Frontiers in Pharmacology, Vol 11 (2021) |
| Publisher Information: |
Frontiers Media S.A., 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
HIV-1, entry inhibitor, inactivator, gp120, gp41, Six-helix bundle, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
Virus inactivator can inactivate cell-free virions without relying on their replication cycle, potentially reducing the impact of viral infection on cells. Previously, we successfully constructed a HIV-1 protein inactivator, 2DLT, by conjugating the D1D2 region of CD4 to the fusion inhibitor T1144 via a 35-amino acid linker. Therefore, it targets both the CD4 binding site in gp120 and NHR region in gp41. Considering that small-molecule agents have the advantages of fast production, low cost, good stability, and oral availability, we herein report the design of a new small-molecule HIV-1 inactivator, FD028, by conjugating FD016 (an analog of NBD-556, a gp120-CD4 binding inhibitor) with FD017 (an analog of 11d, an HIV-1 fusion inhibitor). The results showed that FD028 inactivated cell-free virions at a moderate nanomolar concentration by targeting both HIV-1 gp120 and gp41. Moreover, FD028 has broad-spectrum inhibition and inactivation activity against HIV-1 resistant strains and primary isolates of different subtypes without significant cytotoxicity. Therefore, FD028 has potential for further development as an HIV-1 inactivator-based therapeutic. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1663-9812 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fphar.2020.613361/full; https://doaj.org/toc/1663-9812 |
| DOI: |
10.3389/fphar.2020.613361 |
| Access URL: |
https://doaj.org/article/2b5ec25dc5794553a8b715a38d17d7d5 |
| Accession Number: |
edsdoj.2b5ec25dc5794553a8b715a38d17d7d5 |
| Database: |
Directory of Open Access Journals |
