Inhibitory effect of furanonaphthoquinone derivatives on the replication of Japanese encephalitis virus.
Japanese encephalitis still occurs in endemic and epidemic forms over a wide area of Asia. Although the vaccine against Japanese encephalitis virus (JEV) is widely used, no antiviral drug has been reported. We used several different kinds of furanonaphthoquinone derivatives and found antiviral activity against JEV. Especially, 2-methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) indicated the highest antiviral activity, followed by 2-(1-hydroxyethyl)-, 5(or 8)-hydroxy-, and 2-methyl-5(or 8)-hydroxy-analogs of naphtho[2,3-b]furan-4,9-dione. In the presence of 3 microg/ml FNQ3, the virus yields in Vero cells were 2 x 10(5) PFU/ml at 24 h after infecting with the virus and 10% of the control level. Western blot analysis using anti-E rabbit sera or anti-NS3 showed that the expression of viral proteins was inhibited by treatment with FNQ3. In addition, Northern blot analysis indicated that the appearance of JEV-RNA was also inhibited by FNQ3. These results suggest that FNQ3 inhibits JEV replication through viral RNA and protein synthesis.
Takegami
T
T
Medical Research Institute Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Simamura
E
E
Hirai
K
K
Koyama
J
J
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004664:Encephalitis Virus, Japanese / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000032:analysis; D009285:Naphthoquinones / Q000494:pharmacology*; D020365:RNA Helicases; D012367:RNA, Viral / Q000032:analysis; D012697:Serine Endopeptidases; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000032:analysis; D017361:Viral Nonstructural Proteins / Q000032:analysis; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D008562:Membrane Glycoproteins; D009285:Naphthoquinones; D020365:RNA Helicases; D012367:RNA, Viral; D012697:Serine Endopeptidases; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C106805:2-methylnaphtho(2,3-b)furan-4,9-dione; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C080628:glycoprotein E, Japanese encephalitis virus