1. New antiviral and immunoactivation compounds. Study of molecular mechanisms.

2. Search and study of new antivirals

3. List of viruses

4. Collection of drug-resistant HIV-1 mutants MutantID 50,  M ID 90,  M ISThe level of reduction of sensitivity to drug ddI- resistant 131.23 >380.98 13 10.3 d4T- resistant N 12.23>4.462347.2 d4T- resistant N 2*1.333.5739270 AZT- resistant N 19.0>37.517160.7 AZT- resistant N 26.3631.8124113.6 AZT- resistant N 34.5>37.53380.4 AZT- resistant N 41.4226.210525.4 AZT- resistant N 50.373.744056.6

5. Methods for estimation of anti-HIV activity

6. Anti-HIV activity of the selected derivatives of AZT and d4T (tested compounds were added after virus absorption)

7. Dependence of Anti-HIV activity on time addition of the compounds

8. CONCLUSION 1:

9. FIC 2 indicates antagonism

11. The recombinant integrase protein of HIV-1 (isolate Bru) was prepared by constructing plasmid based on pET15b encoding the integrase gene. We purified IN of HIV-1 by using a bacterial expression system (Escherichia coli).

12. The purified protein was examined using oligonucleotide-based model DNA substrates for the catalytic activities and the kinetic analysis in 3’-processing reaction: Km =(3,7 ± 0,2) 10-10 М, k kat = (1,2 ± 0,3) 10-7 1/s.

13. We have now studied the activity of recombinant HIV-1 integrase on linear 636 bp and 1270 bp double-stranded DNA, containing long terminal repeat (LTR) of HIV-1. The LTR- based model DNA substrates were constructed using circular DNA forms.

14. Specific 3'-end proccessing activity of the 2-LTR substrate by HIV-1 integrase. Specific 3'-end proccessing activity of the 2-LTR substrate by HIV-1 integrase. The 2-LTR substrate was incubated with recombinant HIV- 1 IN for 10 - 60 min at 37oC. The reaction products were analyzed after separation on 20 % urea- polyacrylamide gel. The removal of the labeled 3'-dinucleotide from the 2-LTR substrate by integrase were visualized by autoradiography.

15. Analysis of insertion 1-LTR substrate.

17. Inhibition of recombinant HIV-1 integrase by triterpene’s derivatives

19. Inhibition HIV-1 integrase by triterpene derivatives in 3’-proccessing reaction derivatives in 3’-proccessing reaction

20. M.Stevenson, Immunology, 2003 RNA interference susceptible targets in the HIV-1 replication cycle RNA intermediates during replication of virus, translation of mRNAs and RNA packaging can potentially be targeted by RNA interference (in nuclei ?)

21. Silencing of HIV genes by siRNA % of reduction p24 antigen in HIV-1 infected MT-4 cells Time after transfection 12344* 72 hours 043,230,837,7н.о 96 hours 0-24,715,593 1 –МТ-4 cells transfectd by plasmid Id-hp-pEGFP-NI 2 – МТ-4 cells transfectd by plasmid pr-hp-pEGEP-NI 3 – МТ-4 cells transfectd by plasmid tat-hp-pEGFP-NI 4 – МТ-4 cells transfectd by plasmid RT- hp-pEGFP-NI

22. Antiviral activity of TEDU 5 ’ -phosphonates

23. Study of immunomodulatory activity

24. Effect of niglizin on production of interferon-  (by ELISPOT)

25. Our partners: