Bulletin "Veterinary biotechnology"

Veterynarna biotehnologija – Veterinary biotechnology, 2018, 32(1), 85-91 [in Ukrainian]. https://doi.org/10.31073/vet_biotech32(1)-09

GRYDINA T.L., e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Odessa National Medical University

FEDCHUK A.S., e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Scientific-Research Center "STPP" Ltd.

SHITIKOVA L.I., e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

І.І. Mechnikov Ukrainian Research Anti-Plague Institute

KUZ’MIN V.E., e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ARTEMENKO A.G., e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., BASOK S.S., e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

A.V. Bogatsky Physico-Chemical Institute of the Ukrainian National Academy

GRUZEVSKY A.A., e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Odessa National Medical University

MOLECULAR DESIGN AND DIRECTED SYNTHESIS OF NEW COMPOUNDS WITH ANTIVIRAL ACTIVITY AGAINST AVIAN INFLUENZA VIRUS

Introduction. The influenza virus causes the greatest number of acute respiratory viral infections, which can lead to an exacerbation of chronic systemic diseases, to emergence of bacterial complications, to a significant deterioration of public health.

The goal of the work. The main scope of the investigation was creation of compounds with high activity against avian influenza with the QSAR technology. For the realization of this scope we have to: 1. develop the original software for the QSAR analysis aimed at the molecular design of the compounds with high predicted antiviral activity against avian influenza; 2. conduct directed synthesis of such compounds; 3. determine activity of the new synthesized compounds in vitro against the strain of the avian virus H5N3; 4. compare the experimental anti-influenza activity with the predicted activity calculated with the QSAR technology.

Materials and methods. The anti-influenza activity of the compounds was studied in vitro against the avian virus H5N3 using tissue culture of chorio-allantoic membranes of 10–12-days chicken embryos (CAM).

Results of research and discussion. 25 out of 37 new synthesized compounds have confirmed the high level of predicted activity in the experiment in the tissue of CAM culture. The level of predicted activity of 3 compounds was higher than that obtained in the experiment. The experimental level of anti-influenza activity of 9 compounds exceeded the level of predicted activity. Thus, using the QSAR technologies, synthesis of substances was carried out, which showed 67.57% of the predicted properties in the experiment.

Conclusions and prospects for further research. Models making it possible to establish a quantitative relationship between the structure of compounds and their anti-influenza activity have been developed and applied. The molecular design and directed synthesis of compounds with a high level of predicted activity were carried out with the help of these models. The level of predicted activity was confirmed in the experiment in the tissue of CAM culture against avian influenza H5N3. Application of the proposed approach makes it possible to simplify the search and synthesis of substances that can later be used as antiviral drugs.

Keywords: avian influenza virus, antiviral activity, design and directed synthesis of influenza compounds

REFERENCES

  1. Grydina, T.L. (2015). Likuvannia hrypu – zavzhdy aktualne pytannia [Influenza is always important problem]. Odeskyj medychnyj zhurnal − Odessa med. J., 151, 5, 76–80. [in Ukranian].
  2. World health Report 2002: Reducing risks, promoting healthy life (2002). – Geneva.
  3. Influenza. Bulleten 211, April 2009. www.who.int. Retrieved from: http://www.who.int/mediacentre/factsheets/fs211/ru/index.html
  4. Relevant information about avian influenza virus A (H7N9), provided by the WHO Regional Office updated review of the situation. (2013). www.euro.who.int. Retrieved from http://www.euro.who.int/__data/assets/pdf_file/0011/188534/WHO-Regional-Office-for-Europe-update-on-avian-influenza-AH7N9-virus,-Situation-update-3,-9-May-2013-Rus.pdf.
  5. Avian Influenza. (2018). www.chp.gov.hk. Retrieved from: https://www.chp.gov.hk/files/pdf/2018_avian_influenza_report_vol14_wk01.pdf
  6. Broberg, E., Snacken, R., Adlhoch, C., Beauté, J., Galinska, M., Pereyaslov et al (2015). Start of the 2014/15 influenza season in Europe: drifted influenza A(H3N2) viruses circulate as dominant subtype. Euro Surveill. 20(4), 21023. Retrieved from: http://www. eurosurveillance.org/ViewArticle.aspx?ArticleId=21023
  7. Center of Diesis Control and Prevention. Oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection in two summer campers receiving prophylaxis – North Catolina (2009). MMWR Morb Mortal Wkly Rep.58., 969–720.
  8. Gubareva, L.V. & Hayden, F.G. (2006). M2 and neuraminidase inhibitors: anti-influenza activity, mechanisms of resistance and clinical effectiveness / In: Kawaoka Y, editor. Influenza virology: current topics. Wymondham, United Kingdom: Caister Press., 169–202.
  9. Yen, H.-L., McKimm-Breschkin, J.L., Choy, K.-T., Wong, D.Y., Cheung, P.H., Zhou, J. et al (2013). A resistance to neuraminidase inhibitors conferred by an R292K mutation in a human influenza virus H7N9 isolate can be masked by a mixed R/K viral population. mbio.asm.org. Retrieved from http://mbio.asm.org/content/4/4/e00396–13 (viewed on July 20, 2013).
  10. Stefanov, A.V. (ed.) (2002). Doklinicheskie issledovaniia lekarstvennikh sredstv. Metodicheskie rekomendatsii [Pre-clinical researches of drugs. Methodical recommendations.] Kyiv: Avitsenna. [in Russian].
  11. Ashmarin, I.P. (1959). Vychislenie ЕD50 pri malom chisle podopitnikh zhivotnikh [Calculation of ED50 with a small number of experimental animals]. Zhurnal mikrobiologii − Journal of Microbiology, 2, 102–108. [in Russian].
  12. Gubler, E.V. & Genkin, A.A. (1973). Primenenie neparametricheskikh kriteriev statistiki v medico-biologicheskikh issledovanijakh [Application of nonparametric criteria of statistics in biomedical research]. L: Medicine. [in Russian].

Download full text in PDF