Broad-spectrum and virus-specific nucleic acid-based antivirals against influenza.
Rapid increase in drug-resistant influenza virus isolates, and pandemic threat posed by highly pathogenic avian influenza A and swine flu viruses provide clear and compelling reasons for fast tracking development of novel antiviral drugs. Nucleic acid-based drugs represent a promising class of novel antiviral agents that can be designed to target various seasonal, pandemic and avian influenza viruses. Nucleic acids can be designed to elicit broad-spectrum antiviral responses in the host, by suppressing viral gene expression, or by inducing cleavage or degradation of viral RNA. Immunomodulating nucleic acids, such as double stranded RNA and CpG oligonucleotides, can be potent anti-influenza agents that work by eliciting protective innate and adaptive immunity in the host. By activating the toll-like receptor signaling pathways, these drugs can activate the host's antiviral and inflammatory defenses to combat influenza viruses. Antisense oligonucleotides, small interfering RNAs (siRNA), and nanoRNAs represent sequence specific gene-silencing approaches that could be deployed to suppress or inhibit viral protein gene expression. Lastly, catalytic nucleic acids such as DNAzymes and/or ribozymes can suppress viral replication by repeatedly cleaving viral mRNAs and template RNAs. In summary, nucleic acid-based antiviral agents are versatile, diverse and could complement existing antiviral drugs in combating influenza.
Wong
Jonathan P
JP
Molecular Biology Group, Biotechnology Section, Defence Research and Development Canada - Suffield, Ralston, Alberta, Canada. jonathan.wong@drdc-rddc.gc.ca
Christopher
Mary E
ME
Salazar
Andres M
AM
Sun
Lun-Quan
LQ
Viswanathan
Satya
S
Wang
Ming
M
Saravolac
Edward G
EG
Cairns
Murray J
MJ
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D021881:DNA, Catalytic / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology; D009696:Nucleic Acids / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D012367:RNA, Viral / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051193:Toll-Like Receptors / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D021881:DNA, Catalytic; D009696:Nucleic Acids; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D012367:RNA, Viral; D051193:Toll-Like Receptors