orabase and Influenza--Human

The International Consortium on Anti-Virals (ICAV) is a nonprofit organization that aims to support the development of antivirals for life-threatening and emerging viruses. In recent years, ICAV's emphasis has been predominantly on tropical viruses and avian influenza. The Sixth International Symposium of the ICAV was held at Trent University, Peterborough, Canada, and at MaRs Discovery District, Toronto, Canada, 4-6 May 2008. Approximately 100 participants representing 12 countries attended the symposium. This meeting report focuses on two thought-provoking presentations on topics that require immediate attention: the development of potent broad-spectrum antivirals against emerging viruses and the assessment of the risk of a H5N1 influenza pandemic.

Topics: Animals; Antiviral Agents; Carboxymethylcellulose Sodium; Chickens; Communicable Diseases, Emerging; Disease Outbreaks; Humans; Influenza A Virus, H5N1 Subtype; Influenza in Birds; Influenza, Human; Liposomes; Mice; Peptides; Poultry Diseases; Risk; Virus Diseases; Viruses

Influenza viruses are etiological agents of deadly flu that continue to pose global health threats, and have caused global pandemics that killed millions of people worldwide. The availability of neuraminidase inhibitors and attenuated vaccines improves our ability to defend against influenza, but their benefits can be significantly limited by drug-resistance and virus mutations. Nucleic acid-based drugs may represent a promising class of antiviral agents that could play a role in the prevention and treatment of influenza. Efficacy studies in animals have shown that ds RNA, such as poly ICLC can provide effective and broad-spectrum prophylaxis against lethal challenges against various strains of influenza A virus. Furthermore, similar level of antiviral protection in mice can be provided by using short fragments of oligonucleotides that induce antiviral immunity. Finally, influenza virus expression can also be specifically inhibited or suppressed using antisense oligonucleotides that bind to viral mRNA encoding key viral proteins. The versatility and potency of nucleic acid-based drugs make them potential drug candidates for used in seasonal or pandemic influenza situations.

Topics: Animals; Antiviral Agents; Birds; Carboxymethylcellulose Sodium; Humans; Influenza A virus; Influenza in Birds; Influenza, Human; Liposomes; Mice; Oligodeoxyribonucleotides; Poly I-C; Polylysine

Acute respiratory virus infections such as SARS and pandemic influenza are highly contagious diseases that cause global crisis, and inflict severe human mortality and morbidity. Vaccines against these viruses are either unavailable or do not provide adequate protection. In the absence of effective vaccines, nucleic acid-based immunomodulators have the potential to offer effective, broad-spectrum protection against these deadly pathogens. Poly ICLC and CpG oligonucleotides are promising gene-based drugs which have been shown in animal studies to protect against acute respiratory virus infections. Poly ICLC is a synthetic double-stranded RNA (dsRNA), and an effective interferon-inducer and natural killer cell activator. When encapsulated in liposomes, poly ICLC offers complete protection (100% survival rate in pretreated group versus 0% survival in control group) against a lethal respiratory challenge of influenza A virus in mice. This antiviral effect has been shown to persist for up to 3 weeks post-drug treatment. Poly ICLC pretreatment also protects mice against a respiratory challenge of western equine encephalitis (WEE) virus, at a level comparable to inactivated WEE vaccine. CpG oligos in liposomes also provided high level of protection against the lethal influenza challenge. Together, these studies suggest nucleic acid-based immunomodulators are promising antiviral agents which can offer effective and non-specific protection against acute respiratory virus infections.

Topics: Animals; Carboxymethylcellulose Sodium; CpG Islands; Encephalitis Virus, Western Equine; Encephalomyelitis, Equine; Humans; Influenza A virus; Influenza, Human; Liposomes; Mice; Oligodeoxyribonucleotides; Poly I-C; Polylysine; Respiratory Tract Infections; Virus Diseases