Webbläsaren som du använder stöds inte av denna webbplats. Alla versioner av Internet Explorer stöds inte längre, av oss eller Microsoft (läs mer här: * https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Var god och använd en modern webbläsare för att ta del av denna webbplats, som t.ex. nyaste versioner av Edge, Chrome, Firefox eller Safari osv.

Anti-HIV activity of the small modified amino acid {alpha}-hydroxy glycineamide on in vitro and in vivo HIV-1 capsid assembly and infectivity

In English

Författare

  • Samir Abdurahman
  • Ákos Végvári
  • Masoud Youssefi
  • Michael Levi
  • Stefan Höglund
  • Elin Andersson
  • Peter Horal
  • Bo Svennerholm
  • Jan Balzarini
  • Anders Vahlne

Summary, in English

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.

Publiceringsår

2008

Språk

Engelska

Sidor

3737-3744

Publikation/Tidskrift/Serie

Antimicrobial Agents and Chemotherapy

Volym

52

Issue

10

Dokumenttyp

Artikel i tidskrift

Förlag

American Society for Microbiology

Ämne

  • Medical Engineering

Nyckelord

  • alpha-HGA
  • antiretroviral
  • capsid assembly
  • capsid inhibitor

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1098-6596