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Scientists have found a way to neutralize AIDS

Scientists have found a way to neutralize AIDS
Credit: South Ural State University
Scientists of the South Ural State University and the Institute of Organic Chemistry of Russian Academy of Sciences (IOKh RAS) investigate polysulfur heterocycles—organic compounds that produce antiviral effects and can be used to treat AIDS. The collaboration includes colleagues from the University of Zurich (Switzerland), University College London (UK), the University of North Carolina (U.S.) and the University of Eastern Finland (Finland). One of the latest articles on research has been published in the journal Bioorganic & Medicinal Chemistry Letters (Q1).

Acquired Immunodeficiency Syndrome (AIDS) is a serious disease caused by the human immunodeficiency virus (HIV). AIDS is an incurable disease. It is impossible to completely destroy the virus using methods known at the moment, but scientists around the world are developing drugs that will help cope with this disease.

The laboratory for the synthesis of original polysulfur heterocycles and the search for new compounds with intense and diverse biological activity was established at South Ural State University in 2015, together with the Institute of Organic Chemistry of Russian Academy of Sciences.

"At first we studied the anticancer activity of this class of compounds. But it unexpectedly turned out that such compounds can also have high and selective activity against the immunodeficiency virus of cats, which is the closest analog of the human immunodeficiency virus," says Oleg Rakitin , doctor of chemical sciences, professor.

Scientists have found that compounds of various heterocyclic structures could fight against AIDS. This feature has considerable value for the development of not only chemical but also biological sciences.

"The key scientific result of our research was the discovery of the general mechanism of action of the synthesized polysulfur heterocycles. It consists in the fact that polysulfur heterocycles with a highly reactive sulfur-sulfur (or sulfur-selenium) bond can open in the body with the formation of dithiols, which interact with the zinc atom as if extracting it from the virus molecule in the form of protein-zinc-thiol complexes and thereby deactivating it, " Oleg Rakitin explains.

This kind of action of antiviral drugs was unnoted before. In the course of the work, among the studied compounds, preparations were observed that, together with significant antiviral activity, have low toxicity to ordinary cells. The discovery of this mechanism made it possible to discover new classes of heterocyclic polysulfur compounds as antiviral drugs, as well as the possibility of using these drugs for various viral diseases with a similar type of action.

A distinctive feature of this study is a high degree of collaboration. It was possible to combine together some of the best groups in the world working in various fields of science. Thus, the synthesis and proof of the structure of new compounds took place in a joint laboratory of the Institute of Organic Chemistry of RAS and SUSU, studies of activity against the immunodeficiency virus of cats at the University of Zurich (Switzerland), studies of the mechanism of action of heterocyclic structures at University College London (Great Britain) and the University of North Carolina (U.S.) ), computer simulation of the biological effects of our compounds at the University of Eastern Finland (Finland).

"Recently, a group of researchers from the National Institute of Infectious Diseases (Rio de Janeiro, Brazil) has joined our consortium, which is researching drugs against Sporotrichosis infection, which is especially common in Brazil. It should be noted that each group uses the most modern methods in its research, which allows achieving high results, which are expressed in numerous publications in prestigious journals, " Dr. Rakitin emphasizes.

The research results are presented to the academic community at prestigious conferences, including the American Chemical Society. Currently, scientists are at the stage of searching for optimal structures (with the maximum value of the therapeutic index) for each type of disease. The importance of the results obtained is that the same drugs can be used for various types of diseases (cancer, HIV, etc.), which makes their development interesting in practical terms. The study of the effects of previously synthesized compounds will be extended to treat other diseases with a similar mechanism of action.

More information:
Christopher R.M. Asquith et al. Synthesis and comparison of substituted 1,2,3-dithiazole and 1,2,3-thiaselenazole as inhibitors of the feline immunodeficiency virus (FIV) nucleocapsid protein as a model for HIV infection, Bioorganic & Medicinal Chemistry Letters (2019). DOI: 10.1016/j.bmcl.2019.05.016

Provided by South Ural State University