Mode of action of the anti-influenza virus activity of plant flavonoid, 5,7,4'-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis.
When mouse-adapted influenza virus A/PR/8/34 (A/PR8) (10 PFU/cell) was adsorbed to Madin-Darby canine kidney (MDCK) cells at 4 degrees C for 1 h and incubated at 37 degrees 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 A/PR8 from 4 h to 12 h after incubation by dose-dependent manner and the dose which decrease the virus titer one tenth was 11 microM. F36 (50 microM) did not inhibit the adsorption of A/PR8 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 A/PR8 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 A/PR8 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 A/PR8 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Nagai
T
T
Oriental Medicine Research Center, Kitasato Institute, Tokyo, Japan.
Moriguchi
R
R
Suzuki
Y
Y
Tomimori
T
T
Yamada
H
H
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004285:Dogs; D005419:Flavonoids / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D009980:Influenza A virus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000821:virology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000382:microbiology; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D000998:Antiviral Agents; D005419:Flavonoids; D010936:Plant Extracts; D014764:Viral Proteins; C093385:5,7,4'-trihydroxy-8-methoxyflavone; D009439:Neuraminidase