25 October 2017

Aptamers will protect against HIV

Russian scientists have synthesized a molecule that prevents HIV infection

RIA News

Scientists from the Federal Scientific and Clinical Center of Physico-Chemical Medicine (FNCC FHM) synthesized nucleic acid molecules that prevent infection of body cells with the immunodeficiency virus (HIV). Anna Varizhuk, a researcher at the center, presented the results of her work at the II interdisciplinary scientific conference "Autoimmune and immunodeficiency diseases". The research was supported by a grant from the Russian Science Foundation (RNF).

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The staff of the Laboratory of Artificial antibody synthesis of FNCC FHM are engaged in fundamental research of biochemical processes underlying the development of human diseases. Scientists analyze the mechanisms of rearrangements in the genes of bacteria and viruses (pathogens) that ensure the avoidance of the immune system.

One of the priority areas of work is the study of the human immunodeficiency virus (HIV). Once in the human body, HIV detects immune cells and attaches to their receptors (CD4) with the help of special proteins – glycoproteins.

HIV glycoproteins are usually schematically depicted as protrusions-spikes on the spherical surface of the virus. Joining CD4 triggers the fusion of cell and viral membranes, which is the first stage of infection. Russian biochemists have managed to develop a new aptamer that prevents the fusion of the immunodeficiency virus with the cell.

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The structure of the DNA-aptamer complex with the HIV surface glycoprotein – the results of molecular modeling (modeling was performed by Vladimir Tsvetkov, a researcher at the FNCC FCM). © A.Varizhuk

An aptamer is a short single-stranded fragment of a nucleic acid (DNA or RNA) capable of recognizing certain target molecules and connecting to them.

Single-stranded DNA and RNA can form all kinds of three-dimensional structures: nodes, loops, double and quadruple helices (quadruplexes). A variety of spatial forms, and, accordingly, properties, makes it possible to select suitable aptameric molecules for almost any target: an inorganic compound, protein, peptide, viral particle.

The DNA aptamer created by Russian scientists recognizes the surface glycoprotein of HIV and binds to it. The virus, "blocked" by synthetic DNA, can no longer interact with CD4 receptors of the cell membrane, and infection does not occur.

The development can subsequently be used in the creation of HIV prevention tools, since the aptamer is not toxic to the cells of the human body and at the same time is highly effective. "Obtaining a prototype of the drug is not a very distant prospect. We already have the active substance, it remains to choose a convenient dosage form. I would like to note that our colleagues from the V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences played an important role in the study. The next stage, conducting preclinical and clinical trials, is key. We expect to find partners to promote our development," concluded Anna Varizhuk.

It is worth noting that the cost of synthesizing drugs based on aptamers is several times lower than the cost of producing their protein analogues – antibodies.

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