Inhibition of Influenza Virus Reproduction by Active Components of «Proteflazidum» Flavonoid Composition: Putative Molecular Targets of Interaction
DOI:
https://doi.org/10.15407/microbiolj86.01.026Keywords:
flavonoids, influenza virus, antiviral substances, RNA polymerase, PB2 subunit, molecular dockingAbstract
The search for substances possessing antiviral activities, in particular anti-influenza activity, is of importance for designing new drugs that may be effective in combating viral infections. The antiviral substances of the natural origin such as flavonoids and their derivatives are in the focus of numerous studies. The topical problem is the elucidation of the mechanisms of the interaction between flavonoid substances and the virus-specific targets in infected cells. Aim. To assess the activity of the flavonoid-enriched composition containing the biologically active substances of Proteflazidum against influenza virus in vitro and in vivo and to analyze in silico the putative interactions of the flavonoid components of the composition with PB2 subunit of viral RNA-polymerase. Methods. The anti-influenza effects of flavonoid-enriched composition prepared from the extracts of Deschampsia caespitosa L. and Calamagrostis epigeios L. were assessed in vitro in MDCK cells and in vivo in white outbred mice. Virion RNA was analyzed by RT-PCR with the primers detecting the transcripts of PB1 and PB2 subunits of viral RNA-polymerase and hemagglutinin. The potential interaction of the representative flavonoids of the composition with PB2 subunit of RNA-polymerase was analyzed in silico by molecular docking. Results. The composition under study inhibits effectively replication of А/FM/1/47 (H1N1) strain of influenza virus in vitro and protects the mice against flu infection both in therapeutic and preventive modes of its administration. According to the molecular docking findings, all three major flavonoid compounds of the composition, quercetin, luteolin, and apigenin, interact similarly with the PB2 domain of viral RNA-polymerase. Conclusions. The flavonoid composition containing the biologically active substances of Proteflazidum could be considered as the anti-flu drug with the PB2 subunit of viral RNA-polymerase being one of its potential molecular targets.
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