Inhibition of HIV Maturation via Selective Unfolding and Cross-Linking of Gag Polyprotein by a Mercaptobenzamide Acetylator.
J Am Chem Soc
; 141(20): 8327-8338, 2019 05 22.
Article
en En
| MEDLINE
| ID: mdl-31042030
ABSTRACT
For HIV to become infectious, any new virion produced from an infected cell must undergo a maturation process that involves the assembly of viral polyproteins Gag and Gag-Pol at the membrane surface. The self-assembly of these viral proteins drives formation of a new viral particle as well as the activation of HIV protease, which is needed to cleave the polyproteins so that the final core structure of the virus will properly form. Molecules that interfere with HIV maturation will prevent any new virions from infecting additional cells. In this manuscript, we characterize the unique mechanism by which a mercaptobenzamide thioester small molecule (SAMT-247) interferes with HIV maturation via a series of selective acetylations at highly conserved cysteine and lysine residues in Gag and Gag-Pol polyproteins. The results provide the first insights into how acetylation can be utilized to perturb the process of HIV maturation and reveal a new strategy to limit the infectivity of HIV.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Benzamidas
/
VIH
/
Ensamble de Virus
/
Fármacos Anti-VIH
/
Productos del Gen gag del Virus de la Inmunodeficiencia Humana
/
Desplegamiento Proteico
Límite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos