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In vitro and in silico investigation of interferonogenic analogues of nucleic acids, artificially programmed to block the initial stages of HIV infection of cells

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Abstract

Approaches to the molecular design of antiviral agents based on the principals of adequacy and mimicry to biopolymers have been discussed. The approaches permit for the reproduction of pharmaceutically valuable properties of the polymeric basis (core) and to create novel nongenetic “programs” of bioactivity of macromolecules by means of grafting specific side group combinations to this core. In vivo experiments have shown that the immunostimulating (in particular, interferon-inducing) antiviral potency of nucleic acids (NAs) is a characteristic of carboxylic acid analogues with an NA-type order of furan and anionic component alteration in the polymer chain. Controlled grafting of virus-targeted side groups of the polymeric basis leads to the direct blockage of viral infection in vitro as an additional antiviral effect. In this work, the inhibition of the early penetration stages of human immunodeficiency virus type 1 (HIV-1) in cells has been studied. Modelling of the macromolecule interaction with the most probable target (the virus-cell fusion mediator (an α-helical complex of the N- heptad repeat regions of three HIV-1 envelope glycoprotein gp41 transmembrane molecules) was performed. Computational docking of the experiment in silico resulted in the clarification of the putative mechanisms and parameters for the programming of site-tropic, axial, and belting blockages of the target via the application of an alicyclic-type side group. The discovered opportunities of multipoint axial cobelting blockage of a target opens up new prospects for the prevention/therapy of AIDS, as well as for other viral infections that use similar systems of envelope fusion peptides (of the first and third types) for penetration into cells.

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Authors and Affiliations

  1. Biomodulators and Drugs Research Center, Health Research & Development Foundation, Moscow, 117042, Russia

    A. V. Serbin & V. B. Tsvetkov

  2. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Moscow, 119991, Russia

    A. V. Serbin

  3. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, 119121, Russia

    A. V. Veselovskii & V. B. Tsvetkov

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  1. A. V. Serbin
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  2. A. V. Veselovskii
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Original Russian Text © A.V. Serbin, A.V. Veselovskii, V.B. Tsvetkov, 2012, published in Biotekhnologiya, 2012, No. 1, pp. 72–89.

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Serbin, A.V., Veselovskii, A.V. & Tsvetkov, V.B. In vitro and in silico investigation of interferonogenic analogues of nucleic acids, artificially programmed to block the initial stages of HIV infection of cells. Appl Biochem Microbiol 48, 723–739 (2012). https://doi.org/10.1134/S0003683812090049

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