Antiviral resistance due to deletion in the neuraminidase gene and defective interfering-like viral polymerase basic 2 RNA of influenza A virus subtype H3N2

Trebbien, Ramona; Christiansen, Claus; Fischer, Thea Kølsen

doi:10.1016/j.jcv.2018.02.005

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…In addition, less abundant mutations are not detected since base calling methods currently have a 20% detection threshold [ 20 ]. Despite not being detected through standard methods, low-frequency mutations in viral populations are associated with drug resistance and strain emergence [ 21 – 25 ]. Also low frequency variants have been employed to elucidate transmission directions in viral infections [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Petronella

Ronholm

Suresh³

et al. 2018

BMC Infect Dis

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BackgroundHuman norovirus is the leading cause of viral gastroenteritis globally, and the GII.4 has been the most predominant genotype for decades. This genotype has numerous variants that have caused repeated epidemics worldwide. However, the molecular evolutionary signatures among the GII.4 variants have not been elucidated throughout the viral genome.MethodA metagenomic, next-generation sequencing method, based on Illumina RNA-Seq, was applied to determine norovirus sequences from clinical samples.ResultsHerein, the obtained deep-sequencing data was employed to analyze full-genomic sequences from GII.4 variants prevailing in Canada from 2012 to 2016. Phylogenetic analysis demonstrated that the majority of these sequences belong to New Orleans 2009 and Sydney 2012 strains, and a recombinant sequence was also identified. Genome-wide similarity analyses implied that while the capsid gene is highly diverse among the isolates, the viral protease and polymerase genes remain relatively conserved. Numerous amino acid substitutions were observed at each putative antigenic epitope of the VP1 protein, whereas few amino acid changes were identified in the polymerase protein. Co-infection with other enteric RNA viruses was investigated and the astrovirus genome was identified in one of the samples.ConclusionsOverall this study demonstrated the application of whole genome sequencing as an important tool in molecular characterization of noroviruses.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3419-8) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Petronella

Ronholm

Suresh³

et al. 2018

BMC Infect Dis

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“…Resistance to both classes of influenza antivirals has been reported, with high levels of such resistance rendering adamantanes ineffective (7). Viral mechanisms of resistance to oseltamivir have also been described in certain strains of the influenza A virus (IAV) 2 (8,9). In fact, 98% of the 2009 seasonal H1N1 influenza strains were resistant to oseltamivir, a neuraminidase inhibitor, and over 90% of all circulating viruses in 2005 were resistant to amantadine, the M2 ion channel inhibitor (7, 10 -15).…”

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confidence: 99%

Structural analyses reveal the mechanism of inhibition of influenza virus NS1 by two antiviral compounds

Kleinpeter

Jureka

Falahat

et al. 2018

Journal of Biological Chemistry

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The influenza virus is a significant public health concern causing 250,000-500,000 deaths worldwide each year. Its ability to change quickly results in the potential for rapid generation of pandemic strains for which most individuals would have no antibody protection. This pandemic potential highlights the need for the continuous development of new drugs against influenza virus. As an essential component and well established virulence determinant, NS1 (nonstructural protein 1) of influenza virus is a highly prioritized target for the development of anti-influenza compounds. Here, we used NMR to determine that the NS1 effector domain (NS1) derived from the A/Brevig Mission/1/1918 (H1N1) strain of influenza (1918) binds to two previously described anti-influenza compounds A9 (JJ3297) and A22. We then used X-ray crystallography to determine the three-dimensional structure of the 1918 NS1 Furthermore, we mapped the A9/A22-binding site onto our 1918 NS1 structure and determined that A9 and A22 interact with the NS1 in the hydrophobic pocket known to facilitate binding to the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), suggesting that the two compounds likely attenuate influenza replication by inhibiting the NS1-CPSF30 interaction. Finally, our structure revealed that NS1 could dimerize via an interface that we termed the α-α dimer. Taken together, the findings presented here provide strong evidence for the mechanism of action of two anti-influenza compounds that target NS1 and contribute significant structural insights into NS1 that we hope will promote and inform the development and optimization of influenza therapies based on A9/A22.

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“…However, viruses can become resistant through spontaneous mutations. A deletion at amino acid position 245-248 in the neuraminidase gene of in uenza A virus subtype H3N2 occurred after initiation of treatment with oseltamivir highly reduced its inhibition against oseltamivir (Trebbien et al 2018). The most commonly used method for treating resistant viruses is combination therapy, which uses multiple antivirals in one treatment regimen.…”

Section: Molecular Evolution Of Coronavirusmentioning

confidence: 99%

Genomic and Proteomic Comparative Analysis of SARS-CoV-2 versus SARS-CoV-GD01

Hassanin

Mahgoub

Sitohy

et al. 2020

Preprint

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Background Since the emergence of the pandemic novel pneumonia (COVID-19) disease in Wuhan city in China in November 2019, it is becoming holistically urgent to discover and definitely determine the potential origin of causative virus of this disease, SARS-CoV2 to understand its pathogenic action an better design proper remedies. Methods Using bioinformatics analysis, the whole genome of SARS-CoV2 emerging in 2020 and its deduced proteome were compared with the corresponding information on SARS-CoV-GD01 having emerged in 2003 in China. The genomes squences of the two viruses were obtained from NCBI. Alignment of protein sequences for all genes of both genomes were performed and displayed using Clustal Omega data base. Results Bioinformatics analysis revealed 10 genes encoding 10 proteins in the SARS-CoV2 genome instead of 11 genes encoding 12 proteins in the case of SARS-CoV-GD01, where the first gene is uniquely encoding two glycoproteins. Additionally, bio-informatics analysis disclosed variations in SARS-CoV2 genome size as a result of nucleotides insertion and deletion in all genes of the virus especially orf1ab gene, spike gene, and ORF10 gene. The most conspicuous alteration is apparently noticed in the spike gene, encoding for a novel protein enabling the virus to attach to the cell membrane via the interaction with host cell receptor, initiating probably a new pathway of infection and a specific pathogenic action. This alteration is Conclusions The big alterations in the genome of SARS-CoV-2 from that of SARS-CoV-GD01 may be potentially responsible for the worldwide witnessed high virulence and accelerated spread. The qualified and quantified information presented in the current study on the SARS-CoV-2, detailing the specificity and the magnitude of genomic and proteomic alterations from SARS-CoV-GD01, developed probably during 16 years will not only enable designing right drugs and strategies of confronting the current viral version, but it may rather allow to extrapolate and foresee potential outbreaks of newer versions during the coming decades. At the time of epidemics, nonspecific ways and drugs should be resorted to for confronting emergent viral infections. Chemically modified positively charged proteins and peptides can offer a wealth of potential antiviral agents but need more clinical research.

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Antiviral resistance due to deletion in the neuraminidase gene and defective interfering-like viral polymerase basic 2 RNA of influenza A virus subtype H3N2

Cited by 4 publications

References 31 publications

Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Structural analyses reveal the mechanism of inhibition of influenza virus NS1 by two antiviral compounds

Genomic and Proteomic Comparative Analysis of SARS-CoV-2 versus SARS-CoV-GD01

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