Hemagglutinin variants of influenza A(H1N1)pdm09 virus with reduced affinity for sialic acid receptors

Ayora-Talavera, Guadalupe; Cetina-Montejo, Lisseth; Matos-Patrón, A.; Romero-Beltran, Lesly

doi:10.1007/s00705-013-1934-x

Cited by 6 publications

(5 citation statements)

References 13 publications

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“…These findings suggest that in the cellular environment some mechanism or effects (such as inhibition of other targets, protein–protein interactions, or asymmetric intracellular localization of compounds , ) other than NA inhibition may be involved in the anti-influenza virus (H5N2, H5N6, and H5N8) action. There may also be other uncertainties, for example, host range restriction of influenza virus replication in CEFs. − …”

Section: Resultsmentioning

confidence: 99%

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Structure-Based Optimization of N-Substituted Oseltamivir Derivatives as Potent Anti-Influenza A Virus Agents with Significantly Improved Potency against Oseltamivir-Resistant N1-H274Y Variant

et al. 2018

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Due to the emergence of highly pathogenic and oseltamivir-resistant influenza viruses, there is an urgent need to develop new anti-influenza agents. Herein, five sub-series of oseltamivir derivatives were designed and synthesized to improve their activity towards drug-resistant viral strains by further exploiting the 150-cavity in the neuraminidases (NAs). The bioassay results showed that compound 21h exhibited antiviral activities similar to or better than those of oseltamivir carboxylate (OSC) against H5N1, H5N2, H5N6 and H5N8. Besides, 21h was 5-to 86-fold more potent than OSC toward N1, N8, and N1-H274Y mutant NAs in the inhibitory assays. Computational studies provided a plausible rationale for the high potency of 21h against group-1 and N1-H274Y NAs. In addition, 21h demonstrated acceptable oral bioavailability, low acute toxicity and potent antiviral activity in vivo, and high metabolic stability. Overall, above excellent profiles make 21h a promising drug candidate for the treatment of influenza virus infection.

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Section: Resultsmentioning

confidence: 99%

“…There may also be other uncertainties, for example, host range restriction of influenza virus replication in CEFs. [38][39][40][41] In Vivo Anti-influenza Virus Activity in Specific Pathogen Free (SPF) Chicken…”

Section: Inhibition Of Influenza Neuraminidasesmentioning

confidence: 99%

Structure-Based Optimization of N-Substituted Oseltamivir Derivatives as Potent Anti-Influenza A Virus Agents with Significantly Improved Potency against Oseltamivir-Resistant N1-H274Y Variant

et al. 2018

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“…This virus contained a single mutation, D190Y, at the HA protein. The effect of this mutation on the receptor binding properties of the virus was recently described by our group (Ayora-Talavera et al, 2014). The virus Yuc/3882, isolated by throat swab from patient that subsequently died from the infection, contained two mutations in the receptor binding region of HA, S185N and D222N.…”

Section: Resultsmentioning

confidence: 87%

Amino acid substitution D222N from fatal influenza infection affects receptor-binding properties of the influenza A(H1N1)pdm09 virus

et al. 2015

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We have analyzed the receptor binding profile of A(H1N1)pdm09 recombinant influenza viruses containing the amino acid substitution D222N which has been associated with a fatal case of infection. This mutation was investigated in conjunction with a secondary mutation, S185N. Using human tracheobronchial epithelial cells (HTBE), we found that single mutation D222N affects the binding and replication of the virus during initial stages of infection, with limited but preferred tropism to non-ciliated cells expressing α2,6-SA. However, in conjunction with the S185N change, the (D222N, S185N) virus shows a remarkable increase in binding and replication efficiency, with tropism for both ciliated and non-ciliated cells. Glycan microarray analysis demonstrated correlation between the binding profile and the cell tropism observed in the HTBE cells. These findings suggest that viruses with D222N required compensatory mutations such as S185N to maintain viral fitness, and in combination, affect the pathogenicity of the virus and the clinical outcome.

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“…The effectiveness of a compound/extract/fraction in reducing the plaque size or plaque phenotype can be used as an indicator of its antiviral effect. The synthetic 6′SLN [ 23 ], used as positive control, inhibited virus plaque formation beginning at 10 min of incubation. At different co-treatment times, plaque formation was inhibited by the C4 fraction from E. yucatanensis stem bark as efficiently as observed in the presence of 6′SLN.…”

Section: Discussionmentioning

confidence: 99%

“…MDCK cells were seeded in 12-well plates at a density of 1 × 10 6 cells/well in DMEM supplemented with 10% SFB and incubated for 24 h at 37 °C in 5% CO 2 . The positive control was the influenza virus strain A/MexicoInDRE/797/2010 (MOI = 0.01) and synthetic glycosaccharide 6′SLN (6-sialyl-(N-acetylactosamine) [ 23 ] (Ayora-Talavera et al, 2014). Two mixtures, virus + C4 fraction (3.125 μg/mL) and virus + 6′SLN (157 μg/mL), were incubated at room temperature for six different time intervals (10, 20, 30, 40, 50 and 60 min).…”

Section: Methodsmentioning

confidence: 99%

Bioassay-Guided Fractionation of Erythrostemon yucatanensis (Greenm.) Gagnon & GP Lewis Components with Anti-hemagglutinin Binding Activity against Influenza A/H1N1 Virus

et al. 2022

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Erythrostemon yucatanensis (Greenm.) Gagnon & GP Lewis is a legume tree native to and widely distributed in southeast Mexico, where its branches are used in traditional medicine. An in vitro evaluation of the antiviral activity of extracts and fractions from the leaves, stem bark and roots against two strains of the AH1N1 influenza virus was performed, leading to the identification of bioactive compounds in this medicinal plant. In a cytopathic effect reduction assay, the fractions from the leaves and stem bark were the active elements at the co-treatment level. These were further fractionated based on their hemagglutination inhibition activity. The analysis of spectroscopy data identified a combination of phytosterols (β-sitosterol, stigmasterol and campesterol) in the stem bark active fraction as the main anti-hemagglutinin binding components, while 5-hydroxy-2(2-hydroxy-3,4,5-trimethoxyphenyl)-7-metoxi-4H(chromen-4-ona), which was isolated from the leaf extracts, showed a weak inhibition of viral hemagglutinin. Time of addition experiments demonstrated that the mixture of sterols had a direct effect on viral particle infectivity at the co-treatment level (IC50 = 3.125 µg/mL). This effect was also observed in the virus plaque formation inhibition assay, where the mixture showed 90% inhibition in the first 20 min of co-treatment at the same concentration. Additionally, it was found using qRT-PCR that the NP copy number was reduced by 92.85% after 60 min of co-treatment. These results are the first report of components with anti-hemagglutinin binding activity in the genus Erythrostemon sp.

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Hemagglutinin variants of influenza A(H1N1)pdm09 virus with reduced affinity for sialic acid receptors

Cited by 6 publications

References 13 publications

Structure-Based Optimization of N-Substituted Oseltamivir Derivatives as Potent Anti-Influenza A Virus Agents with Significantly Improved Potency against Oseltamivir-Resistant N1-H274Y Variant

Structure-Based Optimization of N-Substituted Oseltamivir Derivatives as Potent Anti-Influenza A Virus Agents with Significantly Improved Potency against Oseltamivir-Resistant N1-H274Y Variant

Amino acid substitution D222N from fatal influenza infection affects receptor-binding properties of the influenza A(H1N1)pdm09 virus

Bioassay-Guided Fractionation of Erythrostemon yucatanensis (Greenm.) Gagnon & GP Lewis Components with Anti-hemagglutinin Binding Activity against Influenza A/H1N1 Virus

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