Elsevier

Antiviral Research

Volume 26, Issue 1, January 1995, Pages 11-25
Antiviral Research

Research article
Mode of action of the anti-influenza virus activity of plant flavonoid, 5,7,4′-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis

https://doi.org/10.1016/0166-3542(94)00062-DGet rights and content

Abstract

When mouse-adapted influenza virus A/PR/8/34 (APR8) (10 PFU/cell) was adsorbed to Madin-Darby canine kidney (MDCK) cells at 4°C for 1 h and incubated at 37°C, release of the virus from the cells was detected in the medium from 4 h after incubation and reached to plateau at 8 h. However, 5,7,4′-trihydroxy-8-methoxyflavone (F36) from the roots of Scutellaria baicalensis significantly reduced this single-cycle replication of APR8 from 4 h to 12 h after incubation by dose-dependent manner and the dose which decrease the virus titer one tenth was 11 μM. F36 (50 μM) did not inhibit the adsorption of APR8 to MDCK cells, but reduced release of the virus in the medium, when it was added at 0 or 2 h after the incubation. The cell-associated virus determined by sialidase activity was also reduced by F36 treatment at 0 or 2 h. F36 also inhibited the fusion of APR8 with liposomes containing bovine brain mixed gangliosides at pH 5.0. However, F36 little affected on the elongation activity of the viral RNA-dependent RNA polymerase in vitro. These results suggest that F36 reduces the replication of APR8 by inhibiting the fusion of the virus with endosome/lysosome membrane which occurs at early stage of virus infection cycle. Whereas, when F36 was added to the MDCK cells infected with APR8 at 3 or 4 h after incubation, release of the virus in the medium was reduced but the cell-associated virus was increased in comparison with control. Scanning and transmission immunoelectron microscopic studies revealed that F36 inhibited the budding of progeny APR8 from the MDCK cell surface and microvilli, when it was added at 3 h after incubation. The accumulation of the APR8 antigen was observed on the cell surface by immunofluorescence and transmission immunoelectron microscopies by the addition of F36. These results suggest that F36 also shows anti-influenza virus activity against APR8 by inhibiting the budding of the progeny virus from the cell surface, when it was added at budding stage of virus infection cycle.

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