Title: Activity of the small modified amino acid alpha-hydroxy glycinamide on in vitro and in vivo human immunodeficiency virus type 1 capsid assembly and infectivity
Authors: Abdurahman, Samir ×
Végvári, Akos
Youssefi, Masoud
Levi, Michael
Höglund, Stefan
Andersson, Elin
Horal, Peter
Svennerholm, Bo
Balzarini, Jan
Vahlne, Anders #
Issue Date: Oct-2008
Publisher: American Society for Microbiology (ASM)
Series Title: Antimicrobial agents and chemotherapy vol:52 issue:10 pages:3737-44
Abstract: Upon maturation of the HIV-1 virion, proteolytic cleavage of the Gag precursor protein by the viral protease is followed by morphological changes of the capsid protein p24 which will ultimately transform the virus core from an immature spherical to a mature conical structure. Virion infectivity is critically dependent on the just right semi-stability of the capsid cone structure. We have earlier reported that glycineamide (G-NH2) when added to the culture medium of infected cells inhibits HIV-1 replication and that HIV-1 particles with aberrant core structures were formed. Here we show that it is not G-NH2 itself but a metabolite thereof, alpha-hydroxy-glycineamide (alpha-HGA), that is responsible for the antiviral activity. We show that alpha-HGA inhibits the replication of clinical HIV-1 isolates with acquired resistance to reverse transcriptase and protease inhibitors but has no effect on the replication of any of ten different RNA and DNA viruses. alpha-HGA affected the ability of the HIV-1 capsid protein to assemble into tubular or core structures in vitro and in vivo, probably by binding to the hinge region between the N- and C-terminal domains of the HIV-1 capsid protein as indicated by MALDI-MS results. As an antiviral compound, alpha-HGA has an unusually simple structure, a pronounced antiviral specificity and a novel mechanism of antiviral action. As such, it might prove to be a lead compound for a new class of anti-HIV substances.
ISSN: 0066-4804
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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