Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology
(2009) In Retrovirology 6(34).- Abstract
- 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... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1365880
- author
- Abdurahman, Samir ; Végvári, Ákos LU ; Levi, Micheal ; Höglund, Stefan ; Högberg, Marita ; Tong, Weimin ; Romero, Ivan ; Balzarini, Jan and Vahlne, Anders
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Retrovirology
- volume
- 6
- issue
- 34
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000265396300002
- scopus:65449131619
- ISSN
- 1742-4690
- DOI
- 10.1186/1742-4690-6-34
- language
- English
- LU publication?
- yes
- id
- 2bc27576-c6ba-48ef-bb7c-d29e89c8dacd (old id 1365880)
- date added to LUP
- 2016-04-04 12:57:14
- date last changed
- 2022-03-31 20:07:33
@article{2bc27576-c6ba-48ef-bb7c-d29e89c8dacd, abstract = {{Background <br/><br> 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. <br/><br> Results <br/><br> 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 <br/><br> 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. <br/><br> Conclusions <br/><br> 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.}}, author = {{Abdurahman, Samir and Végvári, Ákos and Levi, Micheal and Höglund, Stefan and Högberg, Marita and Tong, Weimin and Romero, Ivan and Balzarini, Jan and Vahlne, Anders}}, issn = {{1742-4690}}, language = {{eng}}, number = {{34}}, publisher = {{BioMed Central (BMC)}}, series = {{Retrovirology}}, title = {{Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology}}, url = {{https://lup.lub.lu.se/search/files/6026185/1369810.pdf}}, doi = {{10.1186/1742-4690-6-34}}, volume = {{6}}, year = {{2009}}, }