Authors: Wong, J. P.; Christopher, M. E.; Viswanathan, S.; Dai, X.; Salazar, A. M.; Sun, L.-Q.; Wang, M.

Source: Current Pharmaceutical Design, Volume 15, Number 11, April 2009 , pp. 1269-1274(6)

Publisher: Bentham Science Publishers

Abstract:

The divergence and antigenic shifts in influenza viruses represent significant challenges for the development of effective vaccines and antiviral drugs against influenza viruses. In view of current challenges and/or deficiencies in the influenza pandemic influenza preparedness, novel antiviral strategies which are robust and can respond to constant viral mutations, are particularly needed to combat future pandemic threats.

Toll-like receptor-3 (TLR-3) is an integral part of the host's innate immune system and serves as an important signaling pathway for the recognition of dsRNA for the triggering of antiviral and inflammatory responses to combat viral infections. This review examines dsRNA including Poly ICLC and liposome-encapsulated Poly ICLC (LE Poly ICLC) as TLR-3 agonists for their antiviral activity against seasonal and highly pathogenic avian influenza (HPAI) viruses. Furthermore, their roles in attenuating the antiviral and inflammatory cytokines in the host will also be explored. Preclinical studies in experimental animals suggest Poly ICLC and liposome-encapsulated Poly ICLC are safe and offer broadspectrum protection against both seasonal and HPAI viruses, as well as other respiratory viruses including respiratory syncytial virus and SARS. Preliminary results from recent studies suggest these drugs up-regulate the production of interferons (-α, -β, and -γ), and tumor necrosis factor (TNF-α) but downregulate some proinflammatory cytokines including IL-2 and IL-4.

Taken together, these results suggest these TLR-3 agonists have a promising role to play as safe, effective and broadspectrum anti-influenza drugs that could complement other antiviral drugs to combat seasonal, zoonotic and pandemic influenza viruses. The clinical safety of these drugs and their efficacy in pre-clinical studies may provide sufficient justification for regulatory agencies to consider their fast track development for use in future outbreaks of pandemic influenza or of other emerging respiratory pathogens.

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161209787846775

Affiliations: 1: Defence R&D Canada - Suffield, Box 4000 Main Station, Medicine Hat, Alberta, Canada T1A 8K6.

Publication date: 2009-04-01

More about this publication?

• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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