Structure and Functions of Influenza Virus Neuraminidase

Gong, Jianzhi; Xu, Wenjian; Zhang, Jie

doi:10.2174/092986707779313444

Cited by 89 publications

(50 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 1918 HA gene was shown to be essential for maximum virus replication and for eliciting a heightened host inflammatory response (16,17,21). The contribution of the 1918 NA gene may, in part, represent the need for optimal balance between sialidase and 1918 HA receptor binding activities and/or previously observed HA cleavage properties (13,14). The increased replication efficiency of the 1918 PB1:Tx/91 (1:7) virus, observed in NHBE cells, was also observed in MDCK cells as distinctly larger plaque size phenotype in comparison with the small plaque phenotype of the 1918 PA:Tx/91 and 1918 PB2:Tx/91 (1:7) reassortants.…”

Section: Construction and Characterization Of Recombinant Viruses Witmentioning

confidence: 99%

“…In addition to the HA and PB1 proteins, the 1957 pandemic influenza virus acquired a neuraminidase (NA) gene of avian origin (7). The NA protein of influenza A virus functions largely in the release of progeny particles (8), thus promoting viral spread, and a pandemic virus bearing a novel avian NA may have a selective advantage by evading immune detection and maintaining compatibility with the newly acquired avian HA (13,14). Much less is known about the origin of the H1N1 virus responsible for the catastrophic influenza pandemic of 1918.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus

Pappas

Aguilar²,

Basler³

et al. 2008

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

143

142

View full text Add to dashboard Cite

Section: Construction and Characterization Of Recombinant Viruses Witmentioning

confidence: 99%

mentioning

confidence: 99%

Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus

Pappas

Aguilar²,

Basler³

et al. 2008

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

143

142

View full text Add to dashboard Cite

“…Firstly, Influenza A virus is susceptible to consistent and unpredictable antigenic variations. 8 This was seen in all the three outbreaks of 1918, 1957 and 1968, in which each of them was caused by different antigenic subtypes of influenza. 12 This kind of antigenic instability renders the treatment and prevention of influenza infection relatively or totally ineffective even in case of vaccinated ones.…”

Section: Introductionmentioning

confidence: 92%

“…Subsequently, influenza viruses cause a contagious respiratory illness that is accompanied by fever, headaches, fatigue, cough and generalized weakness. 8 Sometimes its complications increase when it includes secondary bacterial pneumonia, post-influenza encephalitis, changes in cardiac electrocardiogram and secondary bacterial infections. 9 These viruses not only affects humans but also other species like birds, horses and pigs.…”

Section: Introductionmentioning

confidence: 99%

“…12 This kind of antigenic instability renders the treatment and prevention of influenza infection relatively or totally ineffective even in case of vaccinated ones. 8,13 Secondly, the high incidence of mutations in influenza A virus as a result of antigenic drift and shift led to change in the influenza viruses every 20-30 years which ended up in new, more toxic and drug resistance virus. 9 Moreover, these shifts also made the job of developing anti-influenza virus drugs very difficult due to rapid mutations in the virus.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Energy Based Pharmacophore Modelling and Docking Studies for Determining Potent Inhibitor Against M2 Proton Channel of Influenza Virus

Kanagavelu¹,

Sunny²,

Balasundaram³

et al. 2018

IJPER

View full text Add to dashboard Cite

M2 protein, a crucial glycoprotein present on the viral envelope of Influenza A virus plays an important role in the replication and budding of influenza A virus in the host organism. Due to its primal role in the life cycle of influenza A virus, it is targeted by many potent drugs like amantadine and rimantadine. The emergence of M2 protein mutants in the recent years has rendered these drugs ineffective. Keeping this in our minds, an investigation was performed to determine potent inhibitors of M2 protein using computational strategies like e-pharmacophore based virtual screening and molecular docking. A three dimensional pharmacophore model was generated based on the chemical features using PHASE module of Schrödinger Suite. Subsequently, molecules with same pharmacophoric features were screened from a total of 8621 molecules available in the DrugBank database using the generated pharmacophore hypothesis. This was followed by molecular docking of the screened molecules using three methodologies namely HTVS, SP and XP. Ligand filtration was also done to obtain an efficient collection of hit molecules by analysing pharmacokinetic properties by using Qikprop module. Consequently, our study ascertained nine molecules namely, DB00374, DB00770, DB05015, DB08868, DB00631, DB00983, DB01262, DB00837 and DB01048 which were found to possess anti-viral properties. It is also worth mentioning that antiviral activity of these compounds has been previously reported in recent literature.

show abstract

Phosphonate Congeners of Oseltamivir and Zanamivir as Effective Anti‐influenza Drugs: Design, Synthesis and Biological Activity

Shie

Fang

2013

J Chinese Chemical Soc

View full text Add to dashboard Cite

Influenza is a long-standing health problem. We review here the recent development of neuraminidase inhibitors for influenza treatment. Tamiflu, the phosphate salt of oseltamivir, is an orally available neuraminidase inhibitor designed to have a cyclohexene scaffold to mimic the structure of the oxoniumlike intermediate in the enzymatic cleavage of the terminal sialoside from cell receptor. Many new synthetic procedures of oseltamivir without using shikimic acid have been explored because the current industrial manufacture of tamiflu may have problem in shortage of shikimic acid for global supply during influenza pandemics. In these shikimate-independent syntheses, six different approaches have been utilized to construct the multiple substituted cyclohexene ring: (i) using existing six-membered rings, (ii) construction by Diels-Alder reactions, (iii) construction by intramolecular aldol, Dieckmann and Wittig reactions, (iv) construction by tandem Michael-Wittig reactions, (v) construction by olefin metathesis, and (vi) construction by Claisen rearrangement. Phosphonate group is generally used as a bioisostere of carboxylate in drug design. The syntheses of tamiphosphor and zanaphosphor, which are the phosphonate congeners of oseltamivir and zanamivir, were recently accomplished and shown to possess potent inhibitory activities against avian and human influenza viruses, including the oseltamivir-resistant strain, according to the neuraminidase inhibition, cell-based assay and mice experiments. For the first time, phosphonate monoalkyl esters are proved to be real active drugs, but not prodrugs of the parental phosphonic acids. This review covers the design, synthesis and biological activity of phosphonate compounds as effective anti-influenza agents. Sinica, since 2003. His current interests are organic synthesis and chemical biology, including new synthetic methods, asymmetric catalysis, biomolecular recognition, natural products and drug discovery. Scheme I Outline of the current method for tamiflu manufacture Scheme II Outline of the methods using the existing six-membered rings for oseltamivir synthesis Shie and Fang Scheme V Outline of oseltamivir synthesis involving tandem Michael-Wittig reactions Scheme VI Outline of oseltamivir synthesis involving ring-closure metathesis reaction Scheme VII Outline of oseltamivir synthesis involving Claisen rearrangement Scheme VIII Synthesis of tamiphosphor from D-xylose Scheme IX Synthesis of tamiphosphor and guanidinotamiphosphor from bromobenzene Scheme X Synthesis of tamiphosphor from tamiflu or tamiflu precursor Scheme XI Synthesis of zanamivir from sialic acid Scheme XII Synthesis of zanamivir from D-gluconod-lactone Lipophilicity of oseltamivir phosphonate congenersLipophilicity is an important factor for the pharmacokinetics behavior of drugs. The partition coefficient (P) of Scheme XIII Synthesis of zanamivir via asymmetric nitroaldol reaction Scheme XIV Synthesis of amino-danaphosphor and zanaphosphor from sialic acid

show abstract

Structure and Functions of Influenza Virus Neuraminidase

Cited by 89 publications

References 75 publications

Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus

Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus

Energy Based Pharmacophore Modelling and Docking Studies for Determining Potent Inhibitor Against M2 Proton Channel of Influenza Virus

Phosphonate Congeners of Oseltamivir and Zanamivir as Effective Anti‐influenza Drugs: Design, Synthesis and Biological Activity

Contact Info

Product

Resources

About