Antiviral activity of geneticin against bovine viral diarrhoea virus.
BACKGROUND
Aminoglycoside G418 is commonly used to generate stable replicons for RNA viruses, such as hepatitis C virus, West Nile virus, and bovine viral diarrhoea virus (BVDV). This precludes testing 6418's own antiviral activities against those viruses. Here, we report antiviral activity of 6418 against BVDV.


METHODS
Cell viability and virus yield reduction assays were used to investigate antiviral effects of G418 against BVDV. The expression of viral proteins and RNA were determined by western blot and real-time quantitive PCR, respectively.


RESULTS
We demonstrated that G418 (50% cytotoxicity concentration of 400 microg/ml) improved cell viability of Madin-Darby bovine kidney cells infected with a cytopathic strain of BVDV (NADL) in a dose-dependent manner with 50% effective concentration of 4 microg/ml. Interestingly, close structural analogues with known properties as translation inhibitors similar to G418 - kanamycin and gentamicin - had no antiviral activity against BVDV. In addition, 6418 inhibits virus yield of two different strains of BVDV (NADL and NY-1) without affecting viral RNA replication and translation or viral NS3 protein processing.


CONCLUSIONS
Our data indicate that antiviral activity of G418 could result from interference with either the assembly or release of active virus, rather than the regulation of viral translation and replication. Thus, we propose the use of chemical analogues of G418 as antiviral therapeutics for treatment of viral diseases associated with the Flaviviridae family, such as hepatitis C virus, dengue virus, yellow fever virus, West Nile virus and others.
Birk
Alexander V
AV
Institute of Hepatitis and Viral Research, Doylestown, PA 18902, USA. avbirk@ihvr.org
Dubovi
Edward J
EJ
Zhang
Xianchao
X
Szeto
Hazel H
HH
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000188:drug therapy*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D030241:Diarrhea Virus 1, Bovine Viral / Q000187:drug effects* / Q000502:physiology; D005839:Gentamicins / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology; D007612:Kanamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney / Q000821:virology; D009500:Neutralization Tests; D010447:Peptide Hydrolases / Q000032:analysis; D020365:RNA Helicases / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000032:analysis; D014779:Virus Replication; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000998:Antiviral Agents; D005839:Gentamicins; D007372:Interferons; D007612:Kanamycin; D010447:Peptide Hydrolases; D020365:RNA Helicases; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C100093:gentamicin C; C086730:p80 protein, bovine viral diarrhea virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C001495:bekanamycin; C010680:antibiotic G 418