Comparison of the Activities of Zanamivir, Oseltamivir, and RWJ-270201 against Clinical Isolates of Influenza Virus and Neuraminidase Inhibitor-Resistant Variants

Gubareva, Larisa V.; Webster, Robert G.; Hayden, Frederick G.

doi:10.1128/aac.45.12.3403-3408.2001

Cited by 191 publications

(164 citation statements)

References 30 publications

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“…5) The neuraminidase inhibitor oseltamivir is also compromised due to the emergence of drug-resistant viruses that escape interaction of the inhibitor with the active site of viral neuraminidase. [6][7][8] Antiviral drugs that can inhibit both currently circulating human influenza viruses and avian influenza viruses are therefore urgently needed for future prevention of pandemic influenza.…”

mentioning

confidence: 99%

Glucosyl Hesperidin Prevents Influenza A Virus Replication <i>in Vitro</i> by Inhibition of Viral Sialidase

Saha

Takahashi

Suzuki

2009

Biological & Pharmaceutical Bulletin

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Hesperidin, a flavonoid obtained from citrus fruits, is known to have multiple biological activities and antimicrobial activities for human viruses; however, hesperidin has very low solubility in water and the target molecule of hesperidin for influenza virus remains unknown. A water-soluble derivative of hesperidin, glucosyl hesperidin (GH), which was synthesized by regioselective transglycosylation with cyclodextrin glucanotransferase, has been reported to have biological activities that are as or stronger than those of hesperidin. To determine the inhibitory effect of GH on influenza A virus (IAV) infection, Madin-Darby canine kidney (MDCK) cells were treated with GH before, at the same time as, and after IAV inoculation. GH treatment before IAV inoculation had no effect on virus replication, whereas, treatment with GH at the same time as or after IAV inoculation induced distinct reduction in IAV replication. Inhibition analysis of GH against two surface glycoprotein spikes of IAV revealed that GH prevents IAV replication by inhibition of viral sialidase activity that is involved in the entry and release stages on IAV infection but not by receptor binding inhibition. GH had no cytotoxic effects on MDCK cells in a dose range of 0-25 mM. Our results provide useful information for the development of novel sialidase inhibitors for influenza prevention.

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mentioning

confidence: 99%

Glucosyl Hesperidin Prevents Influenza A Virus Replication <i>in Vitro</i> by Inhibition of Viral Sialidase

Saha

Takahashi

Suzuki

2009

Biological & Pharmaceutical Bulletin

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“…In the current study, it resulted in lower receptor affinity and altered pattern of amino acid binding affinity to Neu5Ac receptor. The same mutation was found to confer both in vitro and in vivo resistance to NA inhibitors [7,16]. However, the effect of such substitution on the structure around it might be minimal [26].…”

Section: Discussionmentioning

confidence: 99%

In-silico structural analysis of the influenza A subtype H7N9 neuraminidase and molecular docking with different neuraminidase inhibitors

Eweas

Abdel‐Moneim

2015

VirusDis.

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Human infection with H7 influenza subtypes usually resulted in mild disease with a rare mortalities, however, human infection with the avian low pathogenic H7N9 influenza virus resulted in about 38.6 % human fatality. Due to the new cross-species barrier of this virus subtype, there is an urgent need to better understand the susceptibility to commercially available antivirals and their relation to the structural changes of the viral neuraminidase. Neuraminidases derived from 2013 H7N9, H5N1 and H1N1 were subjected to a structural analysis of their catalytic and framework binding sites. The modeling structure of selected neuraminidases from H7N9 and influenza A subtypes were solved and the docking studies with oseltamivir, zanamivir, laninamivir and peramivir were conducted. The active site residues that are responsible for both binding and cleavage of the terminally linked sialic acid receptors were found conserved. Docking studies with oseltamivir, zanamivir, laninamivir and peramivir revealed that the laninamivir and peramivir showed superior energy binding activities in comparison to the commonly used oseltamivir and zanamivir. The results presented in the current study provide data that are useful for the future treatment of different influenza A subtypes including the recently emerged H7N9.

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“…In 2008, 86% of circulating H1N1 human virus strains were resistant to oseltamivir (6). Zanamivir (Relenza) inhibits by the same mechanism (24,30) and, similar to oseltamivir, exhibits no toxic, teratogenic, and/or embryocidal effects in animals. However, it is not greatly bioavailable if taken orally and is therefore administered by inhalation, limiting its widespread use.…”

Section: Antiviral Perspectivementioning

confidence: 99%

“…The only FDA-approved small-molecule therapeutics for the treatment of influenza infections are oseltamivir, zanamivir, and the adamantanes. The influenza-specific neuraminidase inhibitors (oseltamivir, zanamivir, and peramivir) prevent release of the virus from infected cells by competing for the enzyme active site with the natural substrate sialic acid found on the surface proteins of normal host cells (30). By blocking the activity of the viral neuraminidase enzyme, neuraminidase inhibitors prevent new viral particles from being released by infected cells.…”

Section: Antiviral Perspectivementioning

confidence: 99%

Adapting global influenza management strategies to address emerging viruses

Noah

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Death by respiratory complications from influenza infections continues to be a major global health concern. Antiviral drugs are widely available for therapy and prophylaxis, but viral mutations have resulted in resistance that threatens to reduce the long-term utility of approved antivirals. Vaccination is the best method for controlling influenza, but vaccine strategies are blunted by virus antigenic drift and shift. Genetic shift in particular has led to four pandemics in the last century, which have prompted the development of efficient global surveillance and vaccination programs. Although the influenza pandemic of 2009 emphasized the need for the rapid standardization of global surveillance methods and the preparation and dissemination of global assay standards for improved reporting and diagnostic tools, outbreaks of novel influenza strains continue to occur, and current efforts must be enhanced by aggressive public education programs to promote increased vaccination rates in the global population. Recently, a novel H7N9 avian influenza virus with potential to become a pandemic strain emerged in China and was transmitted from animals to humans with a demonstrated >20% mortality rate. Sporadic outbreaks of highly lethal avian virus strains have already increased public awareness and altered annual vaccine production strategies to prevent the natural adaption of this virus to human-to-human transmission. Additional strategies for combating influenza include advancement of new antivirals for unexploited viral or host cellular targets; novel adjuvants and alternate vaccine delivery systems; and development of universal protein, DNA, or multivalent vaccines designed to increase immune responsiveness and enhance public health response times.

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Comparison of the Activities of Zanamivir, Oseltamivir, and RWJ-270201 against Clinical Isolates of Influenza Virus and Neuraminidase Inhibitor-Resistant Variants

Abstract: RWJ-270201 is a novel cyclopentane inhibitor of influenza A and B virus neuraminidases (NAs).

Cited by 191 publications

References 30 publications

Glucosyl Hesperidin Prevents Influenza A Virus Replication <i>in Vitro</i> by Inhibition of Viral Sialidase

Glucosyl Hesperidin Prevents Influenza A Virus Replication <i>in Vitro</i> by Inhibition of Viral Sialidase

In-silico structural analysis of the influenza A subtype H7N9 neuraminidase and molecular docking with different neuraminidase inhibitors

Adapting global influenza management strategies to address emerging viruses

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