Research
Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology
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* Corresponding author: Anders Vahlne anders.vahlne@ki.se
1 Division of Clinical Microbiology, Karolinska Institutet, F68 Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden
2 Tripep AB, Hälsovägen 7, SE-141 57 Huddinge, Sweden
3 Department of Electrical Measurements, Lund University, SE-221 00 Lund, Sweden
4 Department of Biochemistry, Uppsala University, SE-751 23 Uppsala, Sweden
5 Chemilia AB, SE-141 83 Huddinge, Sweden
6 Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
Retrovirology 2009, 6:34 doi:10.1186/1742-4690-6-34
Published: 8 April 2009Abstract
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 displays antiviral activity. We show that 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-hydroxy-glycineamide (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 G-NH2-metabolite indeed was α-HGA.
Conclusion
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.