Anti-HIV activity of the small modified amino acid {alpha}-hydroxy glycineamide on in vitro and in vivo HIV-1 capsid assembly and infectivity
(2008) In Antimicrobial Agents and Chemotherapy 52(10). p.3737-3744- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1180938
- author
- Abdurahman, Samir ; Végvári, Ákos LU ; Youssefi, Masoud ; Levi, Michael ; Höglund, Stefan ; Andersson, Elin ; Horal, Peter ; Svennerholm, Bo ; Balzarini, Jan and Vahlne, Anders
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- alpha-HGA, antiretroviral, capsid assembly, capsid inhibitor
- in
- Antimicrobial Agents and Chemotherapy
- volume
- 52
- issue
- 10
- pages
- 3737 - 3744
- publisher
- American Society for Microbiology
- external identifiers
-
- wos:000259480800036
- pmid:18644965
- scopus:54049099240
- pmid:18644965
- ISSN
- 1098-6596
- DOI
- 10.1128/AAC.00265-08
- language
- English
- LU publication?
- yes
- id
- 04535104-e161-4d3c-bf53-b1a98d32074c (old id 1180938)
- date added to LUP
- 2016-04-01 13:04:09
- date last changed
- 2022-03-21 08:22:35
@article{04535104-e161-4d3c-bf53-b1a98d32074c,
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.}},
author = {{Abdurahman, Samir and Végvári, Ákos and Youssefi, Masoud and Levi, Michael and Höglund, Stefan and Andersson, Elin and Horal, Peter and Svennerholm, Bo and Balzarini, Jan and Vahlne, Anders}},
issn = {{1098-6596}},
keywords = {{alpha-HGA; antiretroviral; capsid assembly; capsid inhibitor}},
language = {{eng}},
number = {{10}},
pages = {{3737--3744}},
publisher = {{American Society for Microbiology}},
series = {{Antimicrobial Agents and Chemotherapy}},
title = {{Anti-HIV activity of the small modified amino acid {alpha}-hydroxy glycineamide on in vitro and in vivo HIV-1 capsid assembly and infectivity}},
url = {{https://lup.lub.lu.se/search/files/3142806/1242585.pdf}},
doi = {{10.1128/AAC.00265-08}},
volume = {{52}},
year = {{2008}},
}