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Oligonucleotide inhibitors of HIV-1 integrase efficiently inhibit HIV-1 reverse transcriptase

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Abstract

The impact of conjugates of 11-mer 2′-О-methyl oligoribonucleotides with eosin and 6-carboxy-4,7,2′,4′,5′,7′-hexachlorofluorescein on the functioning of HIV-1 reverse transcriptase (RT) was studied. These compounds were shown to inhibit the activity of RT RNase H domain. The inhibition efficiency was higher for eosin conjugates and did not depend on the oligonucleotide primary structure. The eosin conjugates were also found to block the RT polymerase activity including the mutant proteins resistant to nonnucleoside inhibitors. Since the conjugates are efficient inhibitors of HIV-1 integrase, we can assume that they belong to a new class of HIV-1 dual acting inhibitors, potentially capable of blocking several initial stages of the viral replication cycle.

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Abbreviations

AIDS:

acquired immune deficiency syndrome

Dd:

DNA-dependent

HEX:

6-carboxy-4,7,2′,4′,5′,7′-hexachlorofluorescein

HIV:

human immunodeficiency virus

IN:

integrase

Rd:

RNA-dependent

RT:

reverse transcriptase

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Authors and Affiliations

  1. Chemistry Department and Belozersky Institute of Physico-chemical Biology, Moscow State University, Moscow, 119991, Russia

    S. P. Korolev, T. S. Zatsepin & M. B. Gottikh

Authors
  1. S. P. Korolev
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  2. T. S. Zatsepin
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  3. M. B. Gottikh
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Correspondence to S. P. Korolev.

Additional information

Original Russian Text © S.P. Korolev, T.S. Zatsepin, M.B. Gottikh, 2017, published in Bioorganicheskaya Khimiya, 2017, Vol. 43, No. 2, pp. 157–162.

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Korolev, S.P., Zatsepin, T.S. & Gottikh, M.B. Oligonucleotide inhibitors of HIV-1 integrase efficiently inhibit HIV-1 reverse transcriptase. Russ J Bioorg Chem 43, 135–139 (2017). https://doi.org/10.1134/S1068162017020078

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  • DOI: https://doi.org/10.1134/S1068162017020078

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