Evaluation of synthetic oligonucleotides as inhibitors of West Nile virus replication.
A series of synthetic oligonucleotide phosphorothioate 15-mers were generated against specific sequences in the West Nile virus RNA genome. These antisense oligonucleotides targeted (1) conserved features of the West Nile virus RNA genome that may be expected to lead to inhibition of virus replication since such features play essential roles in the virus lifecycle; (2) G-quartet oligonucleotides with potential facilitated uptake properties and that also targeted conserved sequences among a range of West Nile virus strains. Several formulations with significant in vitro antiviral activity were found. Among the active oligonucleotides were examples that targeted both C-rich RNA sequences of the West Nile RNA genome as well as recognized conserved sequences key to West Nile virus replication. Since the antiviral activity of the latter oligonucleotides diminished upon 2'-O-methyl substitution, it is likely that their activity involves RNase H-catalyzed RNA degradation. One G-rich oligonucleotide that did not target a West Nile virus RNA sequence also was found. These results suggest the potential of antisense strategies for the control of West Nile virus replication if the attendant problem of oligonucleotide delivery can be adequately addressed.
Northern Arizona University, Department of Chemistry and Biochemistry, Bldg 20, Room 125, Box 5698, Flagstaff, AZ 86011, USA. Paul.Torrence@nau.edu
Paul F
PF
Torrence
Nidhi
N
Gupta
Carol
C
Whitney
John D
JD
Morrey
D000818:Animals; D002522:Chlorocebus aethiops; D016376:Oligonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics*; D014902:West Nile virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D016376:Oligonucleotides, Antisense