Influenza: Emergence and Control

Lipatov, A. S.; Govorkova, Elena A.; Webby, Richard J.; Ozaki, Hiroichi; Peiris, Malik; Guan, Yi; Poon, Leo L. M.; Webster, Robert G.

doi:10.1128/jvi.78.17.8951-8959.2004

Cited by 203 publications

(175 citation statements)

References 93 publications

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“…Several anti-influenza compounds have been described in the literature (32). Of those, amantadine and rimantadine act by blocking an ion channel formed by the M2 protein that spans the viral membrane, whereas zanamivir and oseltamivir are specific neuraminidase inhibitors that act by preventing the progeny virus to penetrate the surfaces of infected cells.…”

Section: Discussionmentioning

confidence: 99%

A DNA Aptamer Prevents Influenza Infection by Blocking the Receptor Binding Region of the Viral Hemagglutinin

Jeon¹,

Kayhan²,

Ben-Yedidia³

et al. 2004

Journal of Biological Chemistry

156

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Influenza A virus infection is a major source of morbidity and mortality worldwide. Current means of control for influenza are based on prophylaxis by vaccines and on treatment by the available specific influenza neuraminidase inhibitor drugs. The approach taken in the present study is to prevent and/or ameliorate influenza infection by site-specific blocking of the viral binding to host cell receptors. We describe a novel oligonucleotide, known also as an aptamer, which has been designed to complement the receptor-binding region of the influenza hemagglutinin molecule. It was constructed by screening a DNA library and processing by the selective evolution of ligands by exponential enrichment (SELEX) procedure. We show that this DNA aptamer is indeed capable of inhibiting the hemagglutinin capacity of the virus, as well as in the prevention of viral infectivity in vitro, in tissue culture. Furthermore, it inhibits viral infection by different influenza strains in an animal model, as manifested by 90 -99% reduction of virus burden in the lungs of treated mice. The mode of action of this aptamer is by blocking the binding of influenza virus to target cell receptors and consequently prevention of the virus invasion into the host cells.

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Section: Discussionmentioning

confidence: 99%

A DNA Aptamer Prevents Influenza Infection by Blocking the Receptor Binding Region of the Viral Hemagglutinin

Jeon¹,

Kayhan²,

Ben-Yedidia³

et al. 2004

Journal of Biological Chemistry

156

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show abstract

“…It is widely believed that the emergence of a new influenza pandemic caused by avian strains is only a matter of time and that a safe, effective and easily manufactured vaccine is required [1][2][3]. Pandemic H5N1 vaccine candidates tested to date were manufactured using attenuated reassortant viruses.…”

Section: Introductionmentioning

confidence: 99%

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Kistner

Howard

Spruth

et al. 2007

Vaccine

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The rapid spread and the transmission to humans of avian influenza virus (H5N1) has induced worldwide fears of a new pandemic and raised concerns over the ability of standard influenza vaccine production methods to rapidly supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains were developed and demonstrated to be highly immunogenic in animal models. The vaccines induce cross-neutralising antibodies, highly cross-reactive T-cell responses and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from another clade. These data indicate that cell culture-grown, whole virus vaccines, based on the wild-type virus, allow the rapid high yield production of a candidate pandemic vaccine.

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“…Two of the four antiviral drugs approved in the United States for the treatment and prophylaxis of influenza, amantadine and rimantadine, inhibit the viral M2 ion-channel protein (4); the other two, zanamivir (ZA) and oseltamivir, inhibit the viral neuraminidase (NA) enzymatic activity (5,6). These drugs have limited therapeutic windows, side effects, and high costs (7)(8)(9), and most circulating viruses are already resistant to the M2 inhibitors (10,11). Furthermore, resistance to the NA inhibitors is spreading rapidly (12,13).…”

mentioning

confidence: 99%

Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection

Lee

Weight²,

Haldar³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Covalently conjugating multiple copies of the drug zanamivir (ZA; the active ingredient in Relenza) via a flexible linker to poly-L-glutamine (PGN) enhances the anti-influenza virus activity by orders of magnitude. In this study, we investigated the mechanisms of this phenomenon. Like ZA itself, the PGN-attached drug (PGN-ZA) binds specifically to viral neuraminidase and inhibits both its enzymatic activity and the release of newly synthesized virions from infected cells. Unlike monomeric ZA, however, PGN-ZA also synergistically inhibits early stages of influenza virus infection, thus contributing to the markedly increased antiviral potency. This inhibition is not caused by a direct virucidal effect, aggregation of viruses, or inhibition of viral attachment to target cells and the subsequent endocytosis; rather, it is a result of interference with intracellular trafficking of the endocytosed viruses and the subsequent virusendosome fusion. These findings both rationalize the great antiinfluenza potency of PGN-ZA and reveal that attaching ZA to a polymeric chain confers a unique mechanism of antiviral action potentially useful for minimizing drug resistance.

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Influenza: Emergence and Control

Cited by 203 publications

References 93 publications

A DNA Aptamer Prevents Influenza Infection by Blocking the Receptor Binding Region of the Viral Hemagglutinin

A DNA Aptamer Prevents Influenza Infection by Blocking the Receptor Binding Region of the Viral Hemagglutinin

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Polymer-attached zanamivir inhibits synergistically both early and late stages of influenza virus infection

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