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Abstract
INHIBITION OF RECOMBINANT HUMAN IMMUNODEFICIENCY VIRUS’s INTEGRASE BY NATURAL TRITERPENE DERIVATIVES
E.A. Semenova1, O.A. Plyasunova1, N.I. Petrenko2, V.Z. Petukhova2, E.E. Shults2, G.A. Tolstikov2, A.G. Pokrovsky1
1State Research Center of Virology and Biotechnology “Vector”, Koltsovo, Russia 2Novosibirsk Institute of Organic Chemistry, Novosibirsk, Russia
Integration of human immunodeficiency virus (HIV) DNA into the human genome requires the virus-encoded integrase (IN) protein, and therefore the IN is a suitable target for antiviral strategies. Recently we tested novel natural origin triterpene derivatives (glycyrrhizic and betulinic acids), as inhibitors of recombinant HIV-1 integrase in vitro using traditional oligonucleotide duplex substrate (21 bp), which mimic the retroviral ends. The obtained results show that among seven compounds tested three derivatives inhibit recombinant HIV-1 integrase in the 3’-processing reaction with IC50: glucopyranosyl derivative of glycyrrhizic acid (GlGA)- 37 microM, gamma-amino acid derivative of betulonic acid (N-BA) – 0,4 microM, betulonic acid dipeptide (BAdP) – 0,17 microM. Also these analogues inhibit HIV-1 strain BRU replication on viral infected cell (MT-4) at nontoxic concentrations with IC50: GlGA – 3,1 .10-9 M, N-BA 1,3 .10-6 M, BAdP - 2,6 .10-9 M, and with IS: GlGA – 8887, N-BA - 25, BAdP - 2135. These results suggest that the study of inhibitor’s activity against HIV-1 integrase and more detail investigation of different modifications’ influence on the biological capabilities of natural triterpenes derivatives would allow direct design and creation of new antiviral drugs.
The 2nd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
315
Suggested Citation
" E.A. Semenova , et al.
INHIBITION OF RECOMBINANT HUMAN IMMUNODEFICIENCY VIRUS’s INTEGRASE BY NATURAL TRITERPENE DERIVATIVES.
Poster:
The 2nd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
315"
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