Attaching zanamivir to a polymer markedly enhances its activity against drug-resistant strains of influenza a virus.

J Pharm Sci. 2010 Aug 25;

Authors: Weight AK, Haldar J, Alvarez de Cienfuegos L, Gubareva LV, Tumpey TM, Chen J, Klibanov AM

Effects of the commercial drug zanamivir (Relenza) covalently attached to poly-l-glutamine on the infectivity of influenza A viruses are examined using the plaque reduction assay and binding affinity to viral neuraminidase (NA). These multivalent drug conjugates exhibit (i) up to a 20,000-fold improvement in anti-influenza potency compared with the zanamivir parent against human and avian viral strains, including both wild-type and drug-resistant mutants, and (ii) superior neuraminidase (NA) inhibition constants, especially for the mutants. These findings provide a basis for exploring polymer-attached inhibitors as more efficacious therapeutics, particularly against drug-resistant influenza strains. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.

PMID: 20740680 [PubMed - as supplied by publisher]

NS reassortment of an H7-type HPAIV affects its propagation by altering the regulation of viral RNA production and anti-viral host response.

J Virol. 2010 Aug 25;

Authors: Wang Z, Robb NC, Lenz E, Wolff T, Fodor E, Pleschka S

Highly pathogenic avian influenza viruses (HPAIV) with reassorted NS segments from H5- and H7-type avian virus strains placed in the genetic background of A/FPV/Rostock/34 HAPIV (H7N1) were generated by reverse genetics. Virological characterisations demonstrated that growth kinetics of the reassortant viruses differed from wild type FPV and depended on whether cells were of mammalian or avian origin. Surprisingly, molecular analysis revealed that the different reassortant NS segments were not only responsible for alterations in the anti-viral host response, but furthermore affected viral genome replication and transcription as well as nuclear RNP export. RNP reconstitution experiments demonstrated that the effects on accumulation of viral RNA species was dependent on the specific NS-segment as well as on the genetic background of the RdRp. IFN-beta expression and the induction of apoptosis were found to be inversely correlated with the magnitude of viral growth, while the NS allele, virus subtype and levels of NS1 protein expression showed no correlation. Thus, these results demonstrate that the origin of the NS segment can have a dramatic effect on the replication efficiency and host range of HPAIV. Overall our data suggest that the propagation of NS reassortant influenza viruses is affected at multiple steps of the viral lifecycle as a result of the different activities of the NS1 protein on multiple viral and host functions.

PMID: 20739516 [PubMed - as supplied by publisher]

All that was needed for a pandemic to occur was a genetic mutation in the H5N1 virus that would enable efficient human-to-human transmission. Afterword.

Ann Acad Med Singapore. 2010 Apr;39(4):343-2

Authors: Cutter JL

PMID: 20473465 [PubMed - indexed for MEDLINE]

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Genetic variation of Italian avian paramyxoviruses serotype 9.

Virus Genes. 2010 Aug;41(1):43-6

Authors: Dundon WG, Heidari A, De Nardi R, Terregino C, Capua I, Cattoli G

The haemagglutinin-neuraminidase (HN) and fusion protein (F) gene of four avian paramyoviruses serotype 9 (APMV9) recently isolated from wild birds in Italy have been sequenced. A comparison between the sequences of these four isolates and the prototype virus PMV-9/domestic Duck/New York/22/78 revealed significant sequence variation that suggests that different lineages exist among APMV-9 viruses similar to that seen for APMV-1 (Newcastle disease).

PMID: 20386976 [PubMed - indexed for MEDLINE]

Foreword: this issue of the Seton Hall Law Review presents contributions to Preparing for Pharmaceutical Response to Pandemic Influenza, a two-day Symposium held at Seton hall University School of Law in the fall of 2008.

Seton Hall Law Rev. 2009;39(4):1103-9

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PMID: 20718129 [PubMed - indexed for MEDLINE]