Synthesis and antiviral activity of PB1 component of the influenza A RNA polymerase peptide fragments.

This study is devoted to the antiviral activity of peptide fragments from the PB1 protein - a component of the influenza A RNA polymerase. The antiviral activity of the peptides synthesized was studied in MDCK cell cultures against the pandemic influenza strain A/California/07/2009 (H1N1) pdm09. We found that peptide fragments 6-13, 6-14, 26-30, 395-400, and 531-540 of the PB1 protein were capable of suppressing viral replication in cell culture. Terminal modifications i.e. N-acetylation and C-amidation increased the antiviral properties of the peptides significantly. Peptide PB1 (6-14) with both termini modified showed maximum antiviral activity, its inhibitory activity manifesting itself during the early stages of viral replication. It was also shown that the fluorescent-labeled analog of this peptide was able to penetrate into the cell. The broad range of virus-inhibiting activity of PB1 (6-14) peptide was confirmed using a panel of influenza A viruses of H1, H3 and H5 subtypes including those resistant to oseltamivir, the leading drug in anti-influenza therapy. Thus, short peptide fragments of the PB1 protein could serve as leads for future development of influenza prevention and/or treatment agents.

[Synthesis and study of B-nor-8-isoanalogs of steroid estrogens]. / Sintez i issledovanie B-nor-izoanalogov steroidnykh éstrogenov.

The study of the binding of estradiol B-nor-8-isonalogues to estrogen receptors from the rat uterus helped create the proposed model of the corresponding ligand-receptor complexes. The use of this model ensured the choice of such micromodifications in this steroid group that sharply decreased their hormonal activity. By the example of 16,16-dimethyl-D-homo-B-nor-8-isoestrone, we demonstrated the possibility of the synthesis of the estrogen analogues devoid of uterotropic activity but retaining immunosuppressive activity.