39 results match your criteria oseltamivir-resistant mutants


Effectiveness of favipiravir (T-705) against wild-type and oseltamivir-resistant influenza B virus in mice.

Virology 2020 06 24;545:1-9. Epub 2020 Feb 24.

Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, WHO Collaborating Center for Reference and Research on Influenza, Beijing, 102206, China. Electronic address:

The emergence of resistant mutants to the wildly used neuraminidase inhibitors (NAIs) makes the development of novel drugs necessary. Favipiravir (T-705) is one of the RNA-dependent RNA polymerase (RdRp) inhibitors developed in recent years. To examine the efficacy of T-705 against influenza B virus infections in vivo, C57BL/6 mice infected with wild-type or oseltamivir-resistant influenza B/Memphis/20/96 viruses were treated with T-705. Read More

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Susceptibility of influenza A(H1N1)/pdm2009, seasonal A(H3N2) and B viruses to Oseltamivir in Guangdong, China between 2009 and 2014.

Sci Rep 2017 08 16;7(1):8488. Epub 2017 Aug 16.

Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou, 510640, China.

Nasopharyngeal swabs were collected from patients through the influenza surveillance network of the CDC of Guangdong. All specimens between 2009 and 2014 were checked for influenza virus using MDCK cells and further subtyped. Of those collected, 542 H1N1pdm09, 230 A(H3N2)and 448 B viruses selected at random were subjected to fluorescence-based NAI assays. Read More

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Assessing the oseltamivir-induced resistance risk and implications for influenza infection control strategies.

Infect Drug Resist 2017 20;10:215-226. Epub 2017 Jul 20.

Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan.

Background: Oseltamivir-resistant mutants with higher drug resistance rates and low trans-mission fitness costs have not accounted for influenza (sub)type viruses. Predicting the impacts of neuraminidase inhibitor therapy on infection rates and transmission of drug-resistant viral strains requires further investigation.

Objectives: The purpose of this study was to assess the potential risk of oseltamivir-induced resistance for influenza A (H1N1) and A (H3N2) viruses. Read More

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Sequence analysis of haemagglutinin and neuraminidase of H1N1 strain from a patient coinfected with Mycobacterium tuberculosis.

Mol Cell Probes 2017 08 9;34:59-63. Epub 2017 May 9.

College of Medicine, Taif University, Al-Taif 21944, Saudi Arabia; Virology Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, Egypt. Electronic address:

The 2009 H1N1 pandemic (H1N1pdm09) was associated with a considerable influenza-related morbidity and mortality. Among the complications, Mycobacterial tuberculosis was recorded as a coinfection with influenza in rare cases. The full-length sequences of the viral haemagglutinin and neuraminidase of H1N1pdm09 influenza A virus were analyzed from a recently infected patient. Read More

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Neuraminidase Activity and Resistance of 2009 Pandemic H1N1 Influenza Virus to Antiviral Activity in Bronchoalveolar Fluid.

J Virol 2016 May 14;90(9):4637-4646. Epub 2016 Apr 14.

Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

Unlabelled: Human bronchoalveolar fluid is known to have anti-influenza activity. It is believed to be a frontline innate defense against the virus. Several antiviral factors, including surfactant protein D, are believed to contribute to the activity. Read More

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Antiviral activity of SA-2 against influenza A virus in vitro/vivo and its inhibition of RNA polymerase.

Antiviral Res 2016 Mar 21;127:68-78. Epub 2016 Jan 21.

State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China. Electronic address:

A target-free and cell-based approach was applied to evaluate the anti-influenza properties of six newly synthesized benzoic acid derivatives. SA-2, the ethyl 4-(2-hydroxymethyl-5-oxopyrrolidin-1-yl)-3-[3-(3-methylbenzoyl)-thioureido] benzoate (compound 2) was screened as a potential drug candidate. In a cytopathic effect assay, SA-2 dose dependently inhibited H1N1, H3N2 and the oseltamivir-resistant mutant H1N1-H275Y influenza viruses in both virus-infected MDCK and A549 cells, with 50% effective concentrations (EC50) in MDCK cells of 9. Read More

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Prevalence of Influenza A(H1N1)pdm09 Virus Resistant to Oseltamivir in Shiraz, Iran, During 2012 - 2013.

Jundishapur J Microbiol 2015 Aug 29;8(8):e23690. Epub 2015 Aug 29.

Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, IR Iran.

Background: Oseltamivir has been used as a drug of choice for the prophylaxis and treatment of human influenza A(H1N1)pdm09 infection across the world. However, the most frequently identified oseltamivir resistant virus, influenza A(H1N1)pdm09, exhibit the H275Y substitution in NA gene.

Objectives: This study aimed to determine the prevalence and phylogenetic relationships of oseltamivir resistance in influenza A(H1N1)pdm09 viruses isolated in Shiraz, Iran. Read More

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Molecular docking of potential inhibitors for influenza H7N9.

Comput Math Methods Med 2015 15;2015:480764. Epub 2015 Mar 15.

Medical College, Hunan Normal University, Changsha, Hunan 410013, China.

As a new strain of virus emerged in 2013, avian influenza A (H7N9) virus is a threat to the public health, due to its high lethality and pathogenicity. Furthermore, H7N9 has already generated various mutations such as neuraminidase R294K mutation which could make the anti-influenza oseltamivir less effective or ineffective. In this regard, it is urgent to develop new effective anti-H7N9 drug. Read More

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December 2015

Oseltamivir-resistant influenza A(H1N1)pdm2009 strains found in Brazil are endowed with permissive mutations, which compensate the loss of fitness imposed by antiviral resistance.

Mem Inst Oswaldo Cruz 2015 Feb 27;110(1):101-5. Epub 2015 Feb 27.

Laboratório de Vírus Respiratórios e do Sarampo.

The 2009 pandemic influenza A virus outbreak led to the systematic use of the neuraminidase (NA) inhibitor oseltamivir (OST). Consequently, OST-resistant strains, carrying the mutation H275Y, emerged in the years after the pandemics, with a prevalence of 1-2%. Currently, OST-resistant strains have been found in community settings, in untreated individuals. Read More

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February 2015

Targeting a cluster of arginine residues of neuraminidase to avoid oseltamivir resistance in influenza A (H1N1): a theoretical study.

J Mol Model 2015 Jan 22;21(1). Epub 2015 Jan 22.

Laboratorio de Modelado Molecular y Diseño de Fármacos (Laboratory of Molecular Modeling and Drug Design), Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, 11340, México City, Mexico.

Following the influenza A (H1N1) pandemic in Mexico and around the world in 2009, the numbers of oseltamivir-resistant clinical cases have increased through a mechanism that remains unclear. In this work, we focus on studying the mutated NA structures ADA71175 (GenBank) and 3CKZ (PDB ID). Recently crystallized NA (PDB ID: 3NSS) was used as a wild-type structure and template to construct the three-dimensional (3D) structure of ADA71175. Read More

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January 2015

Mammalian pathogenesis of oseltamivir-resistant pandemic (H1N1) 2009 influenza virus isolated in South Korea.

Virus Res 2014 Jun 19;185:41-6. Epub 2014 Mar 19.

Division of Influenza Virus, Center for Infectious Diseases, Korea National Institute of Health, Osong, Chungcheongbuk-do 363-951, South Korea. Electronic address:

Oseltamivir, a neuraminidase (NA) inhibitor, has been widely used for the treatment of patients infected with the pandemic (H1N1) 2009 influenza virus. With the increasing use of oseltamivir, drug-resistant mutants emerged rapidly and 11 cases of resistant viruses were detected during the 2009 H1N1 pandemic in South Korea. To better understand the differences between oseltamivir-susceptible and oseltamivir-resistant virus, we compared the replication and pathogenesis of the NA H275Y mutant virus, A/Gyeongnam/1820/2009, in ferrets and mice with those of oseltamivir-susceptible A/Korea/01/2009 virus. Read More

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Structural investigation of cycloheptathiophene-3-carboxamide derivatives targeting influenza virus polymerase assembly.

J Med Chem 2013 Dec 13;56(24):10118-31. Epub 2013 Dec 13.

Department of Chemistry and Technology of Drugs, University of Perugia , 06123 Perugia, Italy.

The limited number of drug classes licensed for treatment of influenza virus (Flu), together with the continuous emergence of viral variants and drug resistant mutants, highlights the urgent need to find antivirals with novel mechanisms of action. In this context, the viral RNA-dependent RNA polymerase (RdRP) subunits assembly has emerged as an attractive target. Starting from a cycloheptathiophene-3-carboxamide derivative recently identified by us for its ability to disrupt the interaction between the PA and PB1 subunits of RdRP, we have designed and synthesized a series of analogues. Read More

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December 2013

Impact of potential permissive neuraminidase mutations on viral fitness of the H275Y oseltamivir-resistant influenza A(H1N1)pdm09 virus in vitro, in mice and in ferrets.

J Virol 2014 Feb 20;88(3):1652-8. Epub 2013 Nov 20.

Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, Québec City, QC, Canada.

Neuraminidase (NA) mutations conferring resistance to NA inhibitors (NAIs) generally compromise the fitness of influenza viruses. The only NAI-resistant virus that widely spread in the population, the A/Brisbane/59/2007 (H1N1) strain, contained permissive mutations that restored the detrimental effect caused by the H275Y change. Computational analysis predicted other permissive NA mutations for A(H1N1)pdm09 viruses. Read More

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February 2014

Analysis and assay of oseltamivir-resistant mutants of influenza neuraminidase via direct observation of drug unbinding and rebinding in simulation.

Biochemistry 2013 Nov 30;52(45):8150-64. Epub 2013 Oct 30.

Centre for Computational Chemistry, School of Chemistry, University of Bristol , Bristol BS8 1TS, U.K.

The emergence of influenza drug resistance is a major public health concern. The molecular basis of resistance to oseltamivir (Tamiflu) is investigated using a computational assay involving multiple 500 ns unrestrained molecular dynamics (MD) simulations of oseltamivir complexed with mutants of H1N1-2009 influenza neuraminidase. The simulations, accelerated using graphics processors (GPUs), and using a fully explicit model of water, are of sufficient length to observe multiple drug unbinding and rebinding events. Read More

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November 2013

Different drug-resistant influenza A(H3N2) variants in two immunocompromised patients treated with oseltamivir during the 2011-2012 influenza season in Italy.

J Clin Virol 2013 Sep 27;58(1):132-7. Epub 2013 Jun 27.

S.S. Virologia Molecolare, S.C. Virologia e Microbiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Background: Monitoring the emergence of drug-resistant influenza variants is crucial in influenza surveillance programs.

Objectives: Influenza A kinetics and the emergence of drug-resistant strains in hospitalized patients treated with oseltamivir were investigated.

Study Design: Sequential samples from oseltamivir-treated and -untreated hospitalized patients in the period November 2011 through April 2012 were analyzed. Read More

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September 2013

Oseltamivir-resistant influenza A(H1N1)pdm09 virus in southern Brazil.

Mem Inst Oswaldo Cruz 2013 May;108(3)

Universidade Luterana do Brasil, Canoas, RS, Brasil.

The neuraminidase (NA) genes of A(H1N1)pdm09 influenza virus isolates from 306 infected patients were analysed. The circulation of oseltamivir-resistant viruses in Brazil has not been reported previously. Clinical samples were collected in the state of Rio Grande do Sul (RS) from 2009-2011 and two NA inhibitor-resistant mutants were identified, one in 2009 (H275Y) and the other in 2011 (S247N). Read More

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Pseudovirus-based neuraminidase inhibition assays reveal potential H5N1 drug-resistant mutations.

Authors:
Yi Lu Taijiao Jiang

Protein Cell 2013 May 15;4(5):356-63. Epub 2013 Apr 15.

Key Laboratory of Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

The use of antiviral drugs such as influenza neuraminidase (NA) inhibitors is a critical strategy to prevent and control flu pandemic, but this strategy faces the challenge of emerging drug-resistant strains. For a highly pathogenic avian influenza (HPAI) H5N1 virus, biosafety restrictions have significantly limited the efforts to monitor its drug responses and mechanisms involved. In this study, a rapid and biosafe assay based on NA pseudovirus was developed to study the resistance of HPAI H5N1 virus to NA inhibitor drugs. Read More

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Effect of oseltamivir carboxylate consumption on emergence of drug-resistant H5N2 avian influenza virus in Mallard ducks.

Antimicrob Agents Chemother 2013 May 4;57(5):2171-81. Epub 2013 Mar 4.

Department of Microbiology, Colorado State University, Fort Collins, Colorado, USA.

Oseltamivir carboxylate (OC) has been detected in environmental waters at various levels during recent influenza seasons in humans, reflecting levels of usage and stability of this drug. In consideration of the role of waterfowl as hosts for influenza viruses that may contribute to human infections, we evaluated the effect of consumption of low doses of OC on development of oseltamivir-resistant influenza virus mutants in mallard ducks (Anas platyrhynchos) infected with two different low-pathogenic (LP) H5N2 avian influenza viruses (AIV). We detected development of virus variants carrying a known molecular marker of oseltamivir resistance (neuraminidase E119V) in 4 out of 6 mallards infected with A/Mallard/Minnesota/182742/1998 (H5N2) and exposed to 1,000 ng/liter OC. Read More

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Enhanced mammalian transmissibility of seasonal influenza A/H1N1 viruses encoding an oseltamivir-resistant neuraminidase.

J Virol 2012 Jul 24;86(13):7268-79. Epub 2012 Apr 24.

Division of Infectious Diseases, Mount Sinai School of Medicine, New York, New York, USA.

Between 2007 and 2009, oseltamivir resistance developed among seasonal influenza A/H1N1 (sH1N1) virus isolates at an exponential rate, without a corresponding increase in oseltamivir usage. We hypothesized that the oseltamivir-resistant neuraminidase (NA), in addition to being relatively insusceptible to the antiviral effect of oseltamivir, might confer an additional fitness advantage on these viruses by enhancing their transmission efficiency among humans. Here we demonstrate that an oseltamivir-resistant clinical isolate, an A/Brisbane/59/2007(H1N1)-like virus isolated in New York State in 2008, transmits more efficiently among guinea pigs than does a highly similar, contemporaneous oseltamivir-sensitive isolate. Read More

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Role of permissive neuraminidase mutations in influenza A/Brisbane/59/2007-like (H1N1) viruses.

PLoS Pathog 2011 Dec 8;7(12):e1002431. Epub 2011 Dec 8.

Research Center in Infectious Diseases of the CHUQ-CHUL and Laval University, Québec City, Québec, Canada.

Neuraminidase (NA) mutations conferring resistance to NA inhibitors were believed to compromise influenza virus fitness. Unexpectedly, an oseltamivir-resistant A/Brisbane/59/2007 (Bris07)-like H1N1 H275Y NA variant emerged in 2007 and completely replaced the wild-type (WT) strain in 2008-2009. The NA of such variant contained additional NA changes (R222Q, V234M and D344N) that potentially counteracted the detrimental effect of the H275Y mutation on viral fitness. Read More

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December 2011

High-resolution melting approach to efficient identification and quantification of H275Y mutant influenza H1N1/2009 virus in mixed-virus-population samples.

J Clin Microbiol 2011 Oct 24;49(10):3555-9. Epub 2011 Aug 24.

Molecular Diagnosis Center, National University of Singapore, Singapore, Republic of Singapore.

The single-nucleotide variation 823C to T (His275Tyr), responsible for oseltamivir drug resistance has been detected in some isolates of the influenza A/H1N1/2009 virus. Early detection of the presence of this oseltamivir-resistant strain allows prompt consideration of alternative treatment options. An isolated-probe-asymmetric amplification PCR (Roche LightCycler v2. Read More

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October 2011

Neuraminidase inhibitor R-125489--a promising drug for treating influenza virus: steered molecular dynamics approach.

Biochem Biophys Res Commun 2011 Jul 12;410(3):688-91. Epub 2011 Jun 12.

Institute for Computational Science and Technology, 6 Quarter, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Viet Nam.

Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. Read More

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A comparison of pyrosequencing and neuraminidase inhibition assays for the detection of oseltamivir-resistant pandemic influenza A(H1N1) 2009 viruses.

Antiviral Res 2011 Apr 2;90(1):87-91. Epub 2011 Mar 2.

WHO Collaborating Centre for Reference and Research on Influenza, 10 Wreckyn Street, North Melbourne, VIC 3051, Australia.

Currently most pandemic influenza A(H1N1) 2009 (H1N1pdm) viruses are sensitive to oseltamivir, but a single point mutation (H275Y) in the neuraminidase (NA) gene of H1N1pdm can lead to resistance and such viruses have been reported from several countries. In this study we compare the performance of a pyrosequencing-based method for the detection of the H275Y mutation in H1N1pdm viruses with a conventional NA inhibition assay. Pyrosequencing could detect as little as 5% H275Y mutants in a mixed viral population, while mixtures with 25% or greater mutant virus were required before a significant increase in IC50 value could be detected. Read More

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Frequency of drug-resistant viruses and virus shedding in pediatric influenza patients treated with neuraminidase inhibitors.

Clin Infect Dis 2011 Feb 19;52(4):432-7. Epub 2011 Jan 19.

Division of Virology, Department of Microbiology and Immunology, Institute of MedicalScience, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.

Background: Although influenza virus resistance to the neuraminidase inhibitor zanamivir is reported less frequently than is resistance to the neuraminidase inhibitor oseltamivir in clinical settings, it is unknown whether this difference is due to the limited use of zanamivir or to an inherent property of the drug. We therefore compared the prevalence of drug-resistant viruses and virus shedding in seasonal influenza virus-infected children treated with either oseltamivir or zanamivir.

Methods: Clinical specimens (throat or nasal swab) were collected from a total of 144 pediatric influenza patients during the 2005-2006, 2006-2007, 2007-2008, and 2008-2009 influenza seasons. Read More

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February 2011

Oseltamivir-resistant variants of the 2009 pandemic H1N1 influenza A virus are not attenuated in the guinea pig and ferret transmission models.

J Virol 2010 Nov 25;84(21):11219-26. Epub 2010 Aug 25.

Department of Microbiology, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029-6574, USA.

Oseltamivir is routinely used worldwide for the treatment of severe influenza A virus infection, and should drug-resistant pandemic 2009 H1N1 viruses become widespread, this potent defense strategy might fail. Oseltamivir-resistant variants of the pandemic 2009 H1N1 influenza A virus have been detected in a substantial number of patients, but to date, the mutant viruses have not moved into circulation in the general population. It is not known whether the resistance mutations in viral neuraminidase (NA) reduce viral fitness. Read More

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November 2010

Oseltamivir-resistant pandemic A/H1N1 virus is as virulent as its wild-type counterpart in mice and ferrets.

PLoS Pathog 2010 Jul 22;6(7):e1001015. Epub 2010 Jul 22.

CHUQ-CHUL Research Center in Infectious Diseases and Laval University, Québec City, Québec, Canada.

The neuraminidase inhibitor oseltamivir is currently used for treatment of patients infected with the pandemic A/H1N1 (pH1N1) influenza virus, although drug-resistant mutants can emerge rapidly and possibly be transmitted. We describe the characteristics of a pair of oseltamivir-resistant and oseltamivir-susceptible pH1N1 clinical isolates that differed by a single change (H274Y) in the neuraminidase protein. Viral fitness of pH1N1 isolates was assessed in vitro by determining replication kinetics in MDCK alpha2,6 cells and in vivo by performing experimental infections of BALB/c mice and ferrets. Read More

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Efficacy of the new neuraminidase inhibitor CS-8958 against H5N1 influenza viruses.

PLoS Pathog 2010 Feb 26;6(2):e1000786. Epub 2010 Feb 26.

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Tokyo, Japan.

Currently, two neuraminidase (NA) inhibitors, oseltamivir and zanamivir, which must be administrated twice daily for 5 days for maximum therapeutic effect, are licensed for the treatment of influenza. However, oseltamivir-resistant mutants of seasonal H1N1 and highly pathogenic H5N1 avian influenza A viruses have emerged. Therefore, alternative antiviral agents are needed. Read More

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February 2010

Hark back: passive immunotherapy for influenza and other serious infections.

Crit Care Med 2010 Apr;38(4 Suppl):e66-73

Henry Jackson Foundation, Naval Medical Research Center, Silver Spring, MD, USA.

The world is experiencing a pandemic of swine-origin influenza virus H1N1. A vaccine to prevent disease is now available, and millions have or will become ill before they can be vaccinated. The ability to use swine-origin influenza virus vaccines as a public health tool has been described as a "race against time. Read More

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Molecular prediction of oseltamivir efficiency against probable influenza A (H1N1-2009) mutants: molecular modeling approach.

Amino Acids 2010 Jul;39(2):393-8

Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.

To predict the susceptibility of the probable 2009 influenza A (H1N1-2009) mutant strains to oseltamivir, MD/LIE approach was applied to oseltamivir complexed with the most frequent drug-resistant strains of neuraminidase subtypes N1 and N2: two mutations on the framework residues (N294S and H274Y) and the two others on the direct-binding residues (E119V and R292K) of oseltamivir. Relative to those of the wild type (WT), loss of drug-target interaction energies, especially in terms of electrostatic contributions and hydrogen bonds were dominantly established in the E119V and R292K mutated systems. The inhibitory potencies of oseltamivir towards the WT and mutants were predicted according to the ordering of binding-free energies: WT (-12. Read More

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