Oseltamivir-Resistant Seasonal A(H1N1) and A(H1N1)pdm09 Influenza Viruses from the 2007/2008 to 2012/2013 Season in Nara Prefecture, Japan

Yoneda, Masaki; Okayama, Akira; Kitahori, Yoshiteru

doi:10.7883/yoken.67.385

Cited by 4 publications

(4 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In many countries in the world, the oseltamivir-resistant H275Y mutation development in the NA gene of the influenza viruses depends on usage of oseltamivir and transmission to others. Japan has the highest annual usage of oseltamivir in the world [20] and prevalence we predicted and showed through our study that the prevalence of oseltamivir-resistant A(H1N1)pdmO9 viruses is lower in Mongolia (0%) as compared with developed countries with higher usages of oseltamivir.…”

Section: Discussionmentioning

confidence: 60%

Detection of H275Y Mutation of A(H1N1)pdmO9 Viruses Using a Real-time RT-PCR Assay in Mongolia

Tsedenbal,

Badarch,

Jav

et al. 2016

Cent. Asian j. Med. Sci.

View full text Add to dashboard Cite

Objectives: Oseltamivir is recommended as a first-line drug for the prophylaxis and treatment of influenza A(H1N1)pdmO9 infection worldwide. However, oseltamivir-resistant influenza A(H1N1)pdmO9 viruses have been identified and are mostly associated with an H275Y substitution in the neuraminidase (NA) gene. Careful and rapid laboratory testing for antiviral resistance surveillance of influenza viruses are important to public health and clinical sectors. The aim of our study was to determine oseltamivir-resistant H275Y mutation in clinical specimens by the real-time reverse transcriptase polymerase chain reaction (rtRT-PCR) assay in Mongolia. Methods: A total of 215 clinical specimens tested positive for the A(H1N1)pdmO9 influenza virus by rtRT-PCR. The specimens were collected between January 2013 and August 2014 from patients who visited influenza surveillance sites. All collected specimens were tested for the presence of the oseltamivir-resistant H275Y mutation by rtRT-PCR and DNA sequencing on the NA gene was performed on four of the clinical samples. Results: For all specimens, the H275 (Ct value = 20.4-34.5) was sensitive to oseltamivir by rtRT-PCR assay for detection of the H275Y mutations in the NA gene. Four questionable clinical samples were sequenced for the full NA gene. The data of these samples are available in GISAID influenza virus database with accession numbers EPI533542, EPI462274, EPI462271 and EPI460844. Conclusion: The A(H1 N1)pdm09 viruses were susceptible to oseltamivir during the study period in Mongolia. The rtRT-PCR assay is useful for detection of the H275Y substitution but other possible mutations in the NA gene of the virus could limit the utility of this technique.

show abstract

Section: Discussionmentioning

confidence: 60%

Detection of H275Y Mutation of A(H1N1)pdmO9 Viruses Using a Real-time RT-PCR Assay in Mongolia

Tsedenbal,

Badarch,

Jav

et al. 2016

Cent. Asian j. Med. Sci.

View full text Add to dashboard Cite

show abstract

“…We previously reported that compound 1 is active in this assay with an IC 50 of 549 lM (10). By comparing compound-treated to DMSO-treated cells, we found that six compounds (3,4,5,9,11, and 12) did not possess significant anti-influenza activity in this cell-based assay. (Table 1); however, it was toxic to cells at the upper concentrations tested, which might have skewed the IC 50 curve.…”

Section: Resultsmentioning

confidence: 77%

“…All compounds seemed to bind to the RNA promoter in a fashion similar to compound 1, causing line broadenings of the imino protons of U26, G13, and G24. In addition, some compounds (3,4,5,7,9,11, and 14) also caused line broadening of the imino protons of U27 as compound 1 did ( Figure S1), again indicating that they likely bind to the RNA in a similar fashion as compound 1.…”

Section: Resultsmentioning

confidence: 90%

“…However, H1N1 and H3N2 influenza strains circulating in the North American continent carry a S31N mutation of the M2 protein, which renders them resistant to amantadine (http://www.cdc.gov/flu/about/qa/antiviralresistance for 2013–2014 flu season) . The second class of anti‐influenza drugs includes neuraminidase inhibitors, oseltamivir phosphate (Tamiflu) , and zanamivir (Relenza) , which abolish the release of new virions from the host cell. Unfortunately, neuraminidase‐resistant strains are also emerging.…”

Section: Summary Of Ic50 Cc50 Ic50/cc50 and Kd Values Of Compoundsmentioning

confidence: 99%

See 1 more Smart Citation

Targeting Influenza A Virus RNA Promoter

Bottini

et al. 2015

Chem Biol Drug Des

View full text Add to dashboard Cite

The emergence of drug-resistant strains of influenza virus, makes exploring new classes of inhibitors that target universally conserved viral targets a highly important goal. The influenza A viral genome is made up of 8 single-stranded RNA negative segments. The RNA promoter, consisting of the conserved sequences at the 3′ and 5′ end of each RNA genomic segment, is universally conserved among influenza A virus strains and in all segments. Previously we reported on the identification and NMR structure of DPQ (6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine) (compound 1) in complex with the RNA promoter. Here we report on additional screening and SAR studies with compound 1, including ex vivo anti-influenza activity assays, resulted in improved cellular activity against influenza A virus in the micromolar range.

show abstract

Discovery of Influenza A virus neuraminidase inhibitors using support vector machine and Naïve Bayesian models

Lian

Fang

et al. 2015

Mol Divers

View full text Add to dashboard Cite

Neuraminidase (NA) is a critical enzyme in the life cycle of influenza virus, which is known as a successful paradigm in the design of anti-influenza agents. However, to date there are no classification models for the virtual screening of NA inhibitors. In this work, we built support vector machine and Naïve Bayesian models of NA inhibitors and non-inhibitors, with different ratios of active-to-inactive compounds in the training set and different molecular descriptors. Four models with sensitivity or Matthews correlation coefficients greater than 0.9 were chosen to predict the NA inhibitory activities of 15,600 compounds in our in-house database. We combined the results of four optimal models and selected 60 representative compounds to assess their NA inhibitory profiles in vitro. Nine NA inhibitors were identified, five of which were oseltamivir derivatives with large C-5 substituents exhibiting potent inhibition against H1N1 NA with IC50 values in the range of 12.9-185.0 nM, and against H3N2 NA with IC50 values between 18.9 and 366.1 nM. The other four active compounds belonged to novel scaffolds, with IC50 values ranging 39.5-63.8 μM against H1N1 NA and 44.5-114.1 μM against H3N2 NA. This is the first time that classification models of NA inhibitors and non-inhibitors are built and their prediction results validated experimentally using in vitro assays.

show abstract

Oseltamivir-Resistant Seasonal A(H1N1) and A(H1N1)pdm09 Influenza Viruses from the 2007/2008 to 2012/2013 Season in Nara Prefecture, Japan

Cited by 4 publications

References 16 publications

Detection of H275Y Mutation of A(H1N1)pdmO9 Viruses Using a Real-time RT-PCR Assay in Mongolia

Detection of H275Y Mutation of A(H1N1)pdmO9 Viruses Using a Real-time RT-PCR Assay in Mongolia

Targeting Influenza A Virus RNA Promoter

Discovery of Influenza A virus neuraminidase inhibitors using support vector machine and Naïve Bayesian models

Contact Info

Product

Resources

About