Bifunctional polymeric inhibitors of human influenza A viruses.

Abstract

PURPOSE:

New antiviral agents were prepared by attaching derivatives of sialic acid (1) and of the drug zanamivir (2) to poly(isobutylene-alt-maleic anhydride) (poly-(1 + 2)) or by mixing poly-1 and poly-2, followed by assaying them against wild-type and drug-resistant influenza A Wuhan viruses.

METHODS:

Individually or together, 1 and 2 were covalently bonded to the polymer. The antiviral potencies of the resultant poly-1, poly-2, poly-(1 + 2), and poly-1 + poly-2, as well as 1 and 2, were assessed using plaque reduction assay.

RESULTS:

Attaching 1 to the polymer improved at best millimolar IC(50) values over three orders of magnitude. While 2 exhibited micromolar IC(50) values, poly-2 was >100-fold even more potent. The IC(50) of poly-(1 + 2) against the wild-type strain was >300-fold and approximately 17-fold better than of poly-1 and poly-2, respectively. In contrast, the potency of poly-(1 + 2) vs. poly-2 against the mutant strain merely doubled. The mixture of poly-1 + poly-2 inhibited both viral strains similarly to poly-2.

CONCLUSIONS:

The bifunctional poly-(1 + 2) acts synergistically against the wild-type influenza virus, but not against its drug-resistant mutant, as compared to a physical mixture of the monofunctional poly-1 and poly-2.

• Authors: Jayanta Haldar, Luis Alvarez de Cienfuegos, Terrence M Tumpey, Larisa V Gubareva, Jianzhu Chen, Alexander M Klibanov
• Journal: Pharmaceutical research (Pharm Res) Vol. 27 Issue 2 Pg. 259-63 (Feb 2010) ISSN: 1573-904X [Electronic] United States
• PMID: 20013036 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Polymers

Topics

• Animals
• Antiviral Agents (administration & dosage, chemical synthesis)
• Cell Line
• Chick Embryo
• Dogs
• Humans
• Influenza A virus (drug effects, growth & development)
• Influenza, Human (prevention & control, virology)
• Inhibitory Concentration 50
• Orthomyxoviridae Infections (prevention & control, virology)
• Polymers (administration & dosage, chemical synthesis)
• Viral Plaque Assay