25 December 2018

Defeat the virus

A unique complex for suppressing influenza has been created

Scientists of Tomsk Polytechnic University (TPU) have developed an antiviral composition that has no direct analogues to suppress the expression of influenza A virus genes: PA, NP and NS. The results of the study, published in the journal Antiviral Research, are used to develop a drug for the prevention and treatment of viral infection.

Alexander Timin, a researcher at the TPU Research School of Chemical and Biomedical Technologies, told RIA Novosti that the developed antiviral composition is a combination of three miRNAs (small interfering RNAs) directed at these genes, which are encapsulated in hybrid polyelectrolyte microcapsules.

TPU scientists together with colleagues from the Smorodintsev Influenza Research Institute of the Russian Ministry of Health have developed 11 new miRNAs with antiviral activity in vitro and suppressing conservative and consensus sequences in the genome of the influenza A virus on the NS, PA and NP genes. Antiviral properties were screened and three miRNAs were selected – PA-1630, NP-717 and NS-777, which have the most pronounced inhibitory ability.

In the course of the study, scientists compared the effectiveness of intracellular delivery and the anti-influenza effect of miRNA preparations with a polycationic carrier, liposomes and hybrid microcapsules.

The results showed that miRNA is localized and effectively retained inside capsules with a maximum loading capacity of 6.4 pM/ml of siRNA, which significantly exceeds the capacity for polycationic and liposomal carriers.

Experts analyzed the possibility of using hybrid organic microcapsules with surface SiO2 for this purpose and evaluated them as a means of intracellular delivery of miRNA:

"We have shown that microcapsules effectively protect miRNAs from degradation, which is extremely important for their use as means of intracellular delivery of miRNAs. Their surface can be modified, if necessary, in order to achieve greater biocompatibility, biodegradability, efficiency and targeted delivery," Alexander Timin said.

According to scientists, this can be useful in the development of new pharmaceuticals of various actions.

The study also compared the suppression of influenza virus reproduction in vitro after processing cells with microcapsules containing a mix of three miRNAs and each separately:

"A general decrease in the expression of viral mRNAs, a quantitative decrease in the level of viral target proteins in cells, as well as a decrease in virus reproduction and a decrease in the titer of viral offspring under the action of a "miRNA cocktail" exceeding the similar effect of individual miRNAs were demonstrated," commented Alexander Timin.

The results showed that preventive treatment of cells with a combination of three encapsulated miRNAs causes a strong and specific antiviral effect for influenza A viruses of several subtypes (H1N1, H5N2, H7N9), leading to a decrease in the titer of viral progeny by 2-4 lg TCID50/ml.

According to scientists, the obtained results of the study of the antiviral potential of miRNA will be further used to develop a pharmacological form of a drug based on miRNA intended for the prevention and treatment of viral infection caused by the human influenza A virus.

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