RUDN University chemists created anti-hantavirus drugs 5 times more efficient than existing drugs

RUDN University chemists and their colleagues from Novosibirsk State University, Novosibirsk Institute of Organic Chemistry and The State Research Center of Virology and Biotechnology VECTOR have obtained a new class of compounds that inhibit the replication of the deadly Hantaan virus that affects blood vessels and internal organs of humans. The resulting substances were 5 times more effective than existing antiviral drugs. The results have been published Bioorganic & Medicinal Chemistry Letters.

The Hantaan virus causes acute haemorrhagic fever with renal syndrome (HFRS). The disease is common in the Asian part of Russia, China, Korea, Finland, Sweden, and the countries of eastern and central Europe. The main reservoir and carrier of the virus is the striped field mouse. A human can be infected through the skin or mucous membranes. The virus accumulates and replicates in the blood vessels causing their inflammation, affects the internal organs, primarily the kidneys. The mortality rate varies in different regions from 1% to 10-15%. There are no standard treatment regimens for HFRS -- the treatment is symptomatic. In this regard, the efforts of many scientific groups are focused on the cure development, including the synthesis of new antiviral drugs. RUDN chemists and their colleagues from Novosibirsk synthesized a new class of compounds based on the available natural substances (terpenes), which suppressed the reproduction of the virus in cells 5 times more effective than existing drugs in preliminary experiments.

"The study of antiviral drugs based on terpenes (hydrocarbons, which are found in large quantities in many plants and their essential oils), is very promising. We previously discovered a class of novel terpenoids active against the influenza virus, specifically camphor-based hydrazones. Now our goal is to find new drugs based on natural terpenes with specific activity to viruses causing HFRS", Fedor Zubkov, PhD, Associate Professor at RUDN department of Organic chemistry.

In previous studies chemists have synthesized derivatives of N-acylhydrazones of camphor and fenchone, which were active against smallpox and influenza viruses. One of these substances served as the starting point of this work. The new drug was obtained from natural camphor and fenchone. They can be extracted from the essential oils and resin of conifer trees. Using these substances, chemists obtained terpenic compounds and combined them with a heterocyclic fragment. As a result, a broad library of structurally diverse compounds was obtained - with or without a double bond, additional functional groups in the heterocyclic core, and so on. The composition of the resulting compounds was studied using 2D NMR spectroscopy.

Chemists tested the biological activity of the obtained compounds on pseudovirus system -- a biologically safe virus with the same glycoproteins on its surface as hantavirus. Such a model allows scientists to evaluate the bioactivity faster and safer than using a real virus. Chemists compared the results with the effects of broad-spectrum antiviral drugs Ribavirin and Triazavirin. 12 of the produced drugs demonstrated antiviral activity; one of them was 5 times more effective than Ribavirin and Triazavirin. Chemists concluded that the key structural feature necessary for the effective action of the drug the presence of the isoindole fragment attached to the terpene fragment.

"This class of compounds does not prevent the virus from entering the cell, but it inhibits its intracellular replication. Therefore, we can conclude that the therapeutic target of the obtained terpene complexes is the Hantaan virus protein responsible for replication", Alexandra Antonova, student at RUDN Department of Organic Chemistry.

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