Three years ago, the news spread throughout the world about the spread of the almost incurable Ebola fever. Now they talk less about it, but there is still no medicine against the disease. Therefore, the creation of drugs to combat the virus is still relevant – this is done at the Novosibirsk Institute of Organic Chemistry named after N.N. Vorozhtsov SB RAS jointly with the State Scientific Center of Virology and Biotechnology Vector, the publication Science in Siberia .
Filoviruses Marburg and Ebola are usually studied in parallel – because of the almost identical structure. Both cause high mortality, are transmitted through body fluids, and against them there are no registered medications. In all cases, symptoms do not appear immediately (after about 7-10 days), and all this time a person does not suspect anything, infecting others.
Against these microorganisms, a vaccine already exists: a drug based on antigens or weakened parts of the virus. However, this is not a cure, but prevention: even if the vaccination was done in a timely manner, it does not always help. To effectively combat the disease, scientists from the NIOK SB RAS plan to use inhibitors – substances that block one or another stage of the life cycle of the pathogenic organism.
Typically, the inhibitor is inserted into the virus or binds, for example, to its vital proteins. In a pathogenic organism, everything works like a clock: the slightest interference can lead to disruption of work and cause death. The grant of the RNF was allocated to the development of new effective antiviral drugs with a broader spectrum of activity.
“When a virus enters the body, it goes through several stages: attachment to the host’s cell, penetration, reproduction and access to another cage,” says Candidate of Chemistry Anastasiya Sokolova, a researcher at the NIOH SB RAS. “We are not focused on a specific stage: the main thing is to destroy the virus.”
To create inhibitors, scientists chose two substances: camphor and borneol. The first in its pure form does not exhibit antiviral properties, but if it is added to it, making changes in the structure, it is possible to obtain many compounds against various diseases. Earlier it was confirmed: camphor and borneol derivatives show pronounced antiviral activity against influenza. Recently, Siberian researchers have conducted experiments showing that camphor-based compounds inhibit the Marburg virus on pseudovirus systems (based on recombinant viral particles that are physiologically virtually identical to natural, but biologically safe). Similarity with Ebola suggests a high probability of victory over both microorganisms.
“So far, experiments have been conducted only on pseudovirus systems containing surface glycoproteins (complex proteins) responsible for the entry of the virus into the cell,” explains the researcher. “This approach is safer, and if the compound inhibits this system, there are prerequisites for victory over the pathogenic agent.”
In order to carry out experiments directly with the Marburg and Ebola viruses, the laboratory of the highest biosafety class BSL-4 (Biosafety level) is needed: in Russia such is only available in Novosibirsk at the State Research Center for Virology and Biotechnology Vector. Such studies are very expensive, so only the most promising compounds are tested on real viruses. For this, scientists first synthesize libraries – structurally similar compounds based on borneol or other reagents. After these substances are transferred to biological research, and on their basis are allocated potential inhibitors that can send “fight” with the real virus.
“It’s difficult to answer exactly how these compounds are fighting the virus, because the research has just begun,” Anastasia Sokolova adds. – In order to more or less understand the mechanism of action of the drug against the flu, it took us about five years. Here we work only a year, and while the task is to confirm the effectiveness of the connections. On cells, this has already been done, but on guinea pigs – not yet, so it’s too early to talk about clinical trials. “
Another important benefit of such a study is the prevention of possible bioterrorist attacks: the deliberate use of viruses or bacteria as a means of causing massive diseases.
So, after the completion of the global eradication of smallpox on the Earth and the abolition of vaccination in 1980, more than half of people do not have immunity against orthopoxvirus infections. In 1972, the Biological Weapons Convention was signed, which banned the production and stockpiling of biological weapons, but the risk of bioterrorist attacks still exists.
Cooperation with the University of Leuven in Belgium will give specialists from NIOCH SB RAS the opportunity to conduct more extensive studies of the effectiveness of these compounds. In the framework of the project, in addition to the Marburg and Ebola filoviruses, it is planned to check the library of Siberian scientists for inhibition of the so-called flaviviruses – yellow fever, West Nile fever. They differ in structure and in a set of proteins, which is important, since it is with them that inhibitors are bound. Also, in conjunction with SSC VB “Vector” will be tested inhibitors on the virus of smallpox.
“With low molecular weight (less than 1,000 g / mol) inhibitors in our country and even the world, scientists work quite rarely, which again is associated with a lack of necessary laboratories,” concludes the researcher. “Also, camphor and borneol are relatively inexpensive and non-toxic natural raw materials: these substances have long been used in cosmetics and perfumes.”
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