Место издания:XX Mенделеевский съезд по общей и прикладной химии Ekaterinburg Ekaterinburg
Первая страница:416
Последняя страница:416
Аннотация:Cage compounds display antiviral activity against a broad spectrum of DNA and RNA
viruses. We looked for compounds that are capable to affect orthopoxvirus and influenza
A virus proteins. Various orthopoxviruses encode a family of p37 proteins required for
packaging and distribution of virions. The structure of p37 protein was found in the UniProt
database and it was optimized using molecular dynamics. The best binding site of currently
known blockers (tecovirimat and NIOC-14) was then determined. Docking ofabout 100 cage
compounds to the best binding site was performed.
Anti-influenza activity of adamantane derivatives is based on blocking M2 the ion
channel. Different structures of wild type and mutant M2 channels from the RCSBPDB
database: 2RLF for WT, 2KIH for S31N, 2KWX for V27A – were used for the search of M2
blockers. Optimization of the structure of proteins was performed by the means of molecular
dynamics, potential ligand binding cavities in the dynamic structures of the channel were
found. Docking of nearly 800 compounds revealed 52 structures promising as potential
inhibitors of mutant S31N and V27A and the wild type M2 channel simultaneously.
Based on the docking results a series of new compounds containing cyclic, heterocyclic
or arylcarboxamide fragments; polyfunctional adamantane derivatives containing several
amino, carboxyl or hydroxyl groups, either directly from the adamantane nucleus or on the
periphery of the molecule was synthesized. Testing of antiviral activity was performed in
the SSC VB "Vector". Most of the compounds showed pronounced in vitro activity against
influenza A viruses (H5N1, H3N2) and orthopox viruses (vaccinia virus, cowpox virus, variola
virus, monkeypox virus and ectromelia virus).
The work was supported by the RNF, project 15-13-00084.