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Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology

Författare:
  • Samir Abdurahman
  • Ákos Végvári
  • Micheal Levi
  • Stefan Höglund
  • Marita Högberg
  • Weimin Tong
  • Ivan Romero
  • Jan Balzarini
  • Anders Vahlne
Publiceringsår: 2009
Språk: Engelska
Publikation/Tidskrift/Serie: Retrovirology
Volym: 6
Nummer: 34
Dokumenttyp: Artikel i tidskrift
Förlag: BioMed Central

Sammanfattning

Background

Formation of an HIV-1 particle with a conical core structure is a prerequisite for the subsequent infectivity of the virus particle. We have previously described that glycineamide (G-NH2) when added to the culture medium of infected cells induces non-infectious HIV-1 particles with aberrant core structures.

Results

Here we demonstrate that it is not G-NH2 itself but a metabolite thereof that affects HIV-1 infectivity and capsid assembly. The conversion of G-NH2 to its antiviral metabolite is catalyzed by an enzyme present in bovine and porcine but surprisingly not in human serum. Structure determination by NMR suggested that the active G-NH2 metabolite was α-hydroxyglycineamide (α-HGA). Chemically synthesized α-HGA inhibited HIV-1 replication to the same degree as G-NH2, unlike a number of other synthesized analogues of G-NH2 which had

no effect on HIV-1 replication. Comparisons by capillary electrophoresis and HPLC of the metabolite with the chemically synthesized α-HGA further confirmed that the antiviral GNH2-metabolite indeed was α-HGA.

Conclusions

α-HGA has an unusually simple structure and a novel mechanism of antiviral action. Thus, α-HGA could be a lead for new antiviral substances belonging to a new class of anti-HIV drugs, i.e. capsid assembly inhibitors.

Nyckelord

  • Medical Engineering

Övriga

Published
  • ISSN: 1742-4690

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