| Autor: |
Daniel Adu-Ampratwum, Yuhan Pan, Pratibha C. Koneru, Janet Antwi, Ashley C. Hoyte, Jacques Kessl, Patrick R. Griffin, Mamuka Kvaratskhelia, James R. Fuchs, Ross C. Larue |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
ACS Omega, Vol 7, Iss 5, Pp 4482-4491 (2022) |
| ISSN: |
2470-1343 |
| Popis: |
Human immunodeficiency virus-1 (HIV-1) is the causative agent of acquired immunodeficiency syndrome (AIDS). HIV-1, like all retroviruses, stably integrates its vDNA copy into host chromatin, a process allowing for permanent infection. This essential step for HIV-1 replication is catalyzed by viral integrase (IN) and aided by cellular protein LEDGF/p75. In addition, IN is also crucial for proper virion maturation as it interacts with the viral RNA genome to ensure encapsulation of ribonucleoprotein complexes within the protective capsid core. These key functions make IN an attractive target for the development of inhibitors with various mechanisms of action. We conducted a high-throughput screen (HTS) of ∼370,000 compounds using a homogeneous time-resolved fluorescence-based assay capable of capturing diverse inhibitors targeting multifunctional IN. Our approach revealed chemical scaffolds containing diketo acid moieties similar to IN strand transfer inhibitors (INSTIs) as well as novel compounds distinct from all current IN inhibitors including INSTIs and allosteric integrase inhibitors (ALLINIs). Specifically, our HTS resulted in the discovery of compound |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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