Influenza Neuraminidase Inhibitors: Synthetic Approaches, Derivatives and Biological Activity

Laborda, Pedro; Wang, Suyan; Voglmeir, Josef

doi:10.3390/molecules21111513

Cited by 65 publications

(59 citation statements)

References 139 publications

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“…41 In principle, preventing a viral pathogen from entering the host cell represents the ideal antiviral strategy because the virus is not allowed to ''hack'' the host: IFV NAIs have been successfully used to competitively bind the sialic acid-binding pocket of neuroaminidase and are good examples of this approach. Oseltamivir and zanamivir have been used as anti-flu therapies, 42 whereas laninamivir and peramivir show antiviral activity against wild-type but also against oseltamivir-resistant and NAI-resistant strains, respectively. 43,44 The nonenveloped rhinoviruses use viral capsid structures to bind their receptors (intercellular adhesion molecule 1 [ICAM-1], low-density lipoprotein receptor, and cadherin-related family member 3).…”

Section: Immune and Antiviral Pathway Modulatorsmentioning

confidence: 99%

Promising approaches for the treatment and prevention of viral respiratory illnesses

Papadopoulos

Megremis

Kitsioulis

et al. 2017

Journal of Allergy and Clinical Immunology

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Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses.

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Section: Immune and Antiviral Pathway Modulatorsmentioning

confidence: 99%

Promising approaches for the treatment and prevention of viral respiratory illnesses

Papadopoulos

Megremis

Kitsioulis

et al. 2017

Journal of Allergy and Clinical Immunology

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“…The synthesis of mannosamine and sialic acid derivatives is one of the main limitations in studying them as potential inhibitors of the sialic acid metabolic pathway [32][33][34][35][36][37]. In this field, several research groups have reported the synthesis of mannosamine derivatized with N-linked aliphatic chains.…”

Section: Chemoenzymatic Synthesis Of Mannosamine and Sialic Acid Derimentioning

confidence: 99%

N-acetylglucosamine 2-Epimerase from Pedobacter heparinus: First Experimental Evidence of a Deprotonation/Reprotonation Mechanism

Wang

Laborda

et al. 2016

Catalysts

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Abstract:The control of cellular N-acetylmannosamine (ManNAc) levels has been postulated to be an effective way to modulate the decoration of cell surfaces with sialic acid. N-acetylglucosamine 2-epimerase catalyzes the interconversion of N-acetylglucosamine (GlcNAc) and ManNAc. Herein, we describe the cloning, expression, purification and biochemical characterization of an unstudied N-acetylglucosamine 2-epimerase from Pedobacter heparinus (PhGn2E). To further characterize the enzyme, several N-acylated glucosamine derivatives were chemically synthesized, and subsequently used to test the substrate specificity of PhGn2E. Furthermore, NMR studies of deuterium/hydrogen exchange at the anomeric hydroxy group and C-2 positions of the substrate in the reaction mixture confirmed for the first time the postulated epimerization reaction via ring-opening/enolate formation. Site-directed mutagenesis of key residues in the active site showed that Arg63 and Glu314 are directly involved in proton abstraction and re-incorporation onto the substrate. As all mechanistically relevant active site residues also occur in all mammalian isoforms, PhGn2E can serve as a model N-acetylglucosamine 2-epimerase for further elucidation of the active site mechanism in these enzymes.

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“…Due to the specific activity of NA, inhibitors work effectively against influenza A and B viruses. Oseltamivir, zanamivir, peramivir, and laninamivir are long-acting neuraminidase inhibitors for the treatment and prophylaxis of human influenza virus infection [39,40]. Between the NA inhibitors of oseltamivir phosphate (Tamiflu ® ) and zanamivir (Relenza ® ), the former is considered the most effective because of its higher bioavailability (30-100%) [25].…”

Section: Discussionmentioning

confidence: 99%

Experimental Infection Using Mouse-Adapted Influenza B Virus in a Mouse Model

Prokopyeva

Kurskaya

Sobolev

et al. 2020

Viruses

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Every year, influenza B viruses (IBVs) contribute to annual illness, and infection can lead to serious respiratory disease among humans. More attention is needed in several areas, such as increasing virulence or pathogenicity of circulating B viruses and developing vaccines against current influenza. Since preclinical trials of anti-influenza drugs are mainly conducted in mice, we developed an appropriate infection model, using an antigenically-relevant IBV strain, for furtherance of anti-influenza drug testing and influenza vaccine protective efficacy analysis. A Victoria lineage (clade 1A) IBV was serially passaged 17 times in BALB/c mice, and adaptive amino acid substitutions were found in hemagglutinin (HA) (T214I) and neuraminidase (NA) (D432N). By electron microscopy, spherical and elliptical IBV forms were noted. Light microscopy showed that mouse-adapted IBVs caused influenza pneumonia on day 6 post inoculation. We evaluated the illness pathogenicity, viral load, and histopathological features of mouse-adapted IBVs and estimated anti-influenza drugs and vaccine efficiency in vitro and in vivo. Assessment of an investigational anti-influenza drug (oseltamivir ethoxysuccinate) and an influenza vaccine (Ultrix ® , SPBNIIVS, Saint Petersburg, Russia) showed effectiveness against the mouse-adapted influenza B virus.

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Influenza Neuraminidase Inhibitors: Synthetic Approaches, Derivatives and Biological Activity

Cited by 65 publications

References 139 publications

Promising approaches for the treatment and prevention of viral respiratory illnesses

Promising approaches for the treatment and prevention of viral respiratory illnesses

N-acetylglucosamine 2-Epimerase from Pedobacter heparinus: First Experimental Evidence of a Deprotonation/Reprotonation Mechanism

Experimental Infection Using Mouse-Adapted Influenza B Virus in a Mouse Model

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