1,333 results match your criteria oseltamivir resistance


An influenza A(H5N8) virus isolated during an outbreak at a poultry farm in Russia in 2017 has an N294S substitution in the neuraminidase and shows reduced susceptibility to oseltamivir.

Antiviral Res 2021 Apr 29;191:105079. Epub 2021 Apr 29.

State Research Center of Virology and Biotechnology "Vector" Rospotrebnadzor, Koltsovo, Novosibirsk Region, 630559, Russian Federation.

This study aimed to assess the antiviral susceptibility of influenza A(H5N8) viruses isolated in Russia in 2014-2018. Genetic analysis of 57 Russian isolates with full genome sequences did not find any markers of reduced susceptibility to baloxavir. Only one strain bore an amino acid substitution associated with adamantane resistance (M2-S31N). Read More

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Antivirals Targeting the Surface Glycoproteins of Influenza Virus: Mechanisms of Action and Resistance.

Viruses 2021 04 6;13(4). Epub 2021 Apr 6.

State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, 195 Dongfengxi Rd, Guangzhou 510182, China.

Hemagglutinin and neuraminidase, which constitute the glycoprotein spikes expressed on the surface of influenza A and B viruses, are the most exposed parts of the virus and play critical roles in the viral lifecycle. As such, they make prominent targets for the immune response and antiviral drugs. Neuraminidase inhibitors, particularly oseltamivir, constitute the most commonly used antivirals against influenza viruses, and they have proved their clinical utility against seasonal and emerging influenza viruses. Read More

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Nanoparticle composite TPNT1 is effective against SARS-CoV-2 and influenza viruses.

Sci Rep 2021 04 22;11(1):8692. Epub 2021 Apr 22.

Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Rd., Taipei, 10002, Taiwan.

A metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ppm), ZnO-NP (60 ppm) and ClO (42.5 ppm) in aqueous solution was prepared and characterized by spectroscopy, transmission electron microscopy, dynamic light scattering analysis and potentiometric titration. Based on the in vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with effective concentration within the range to be used as food additives. Read More

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Detection of variants with reduced baloxavir marboxil and oseltamivir susceptibility in children with influenza A during the 2019-2020 influenza season.

J Infect Dis 2021 Apr 10. Epub 2021 Apr 10.

Department of Pediatrics, Fukushima Medical University, Fukushima, Japan.

Background: We aimed to detect influenza variants with reduced susceptibility to baloxavir marboxil (baloxavir) and oseltamivir and identify differences in the clinical course between children with and without these variants after anti-viral treatment.

Methods: During the 2019-2020 influenza season, we enrolled children with confirmed influenza A (20 treated with baloxavir and 16 with oseltamivir). We analyzed patients' sequential viral RNA loads and infectious virus titers, the drug susceptibilities of clinical isolates, and amino acid substitutions in the viral polymerase acidic protein subunits or neuraminidase. Read More

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Repurposed drugs block toxin-driven platelet clearance by the hepatic Ashwell-Morell receptor to clear bacteremia.

Sci Transl Med 2021 Mar;13(586)

Biomedical Sciences Graduate Program, UC San Diego, La Jolla, CA 92093, USA.

(SA) bloodstream infections cause high morbidity and mortality (20 to 30%) despite modern supportive care. In a human bacteremia cohort, we found that development of thrombocytopenia was correlated to increased mortality and increased α-toxin expression by the pathogen. Platelet-derived antibacterial peptides are important in bloodstream defense against SA, but α-toxin decreased platelet viability, induced platelet sialidase to cause desialylation of platelet glycoproteins, and accelerated platelet clearance by the hepatic Ashwell-Morell receptor (AMR). Read More

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Adverse Effects of Oseltamivir Phosphate Therapy on the Liver of LDLR-/- Mice Without Any Benefit on Atherosclerosis and Thrombosis.

J Cardiovasc Pharmacol 2021 May;77(5):660-672

UMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), Université de Reims Champagne Ardenne (URCA), UFR Sciences Exactes et Naturelles, Reims, France.

Abstract: Desialylation, governed by sialidases or neuraminidases, is strongly implicated in a wide range of human disorders, and accumulative data show that inhibition of neuraminidases, such as neuraminidases 1 sialidase, may be useful for managing atherosclerosis. Several studies have reported promising effects of oseltamivir phosphate, a widely used anti-influenza sialidase inhibitor, on human cancer cells, inflammation, and insulin resistance. In this study, we evaluated the effects of oseltamivir phosphate on atherosclerosis and thrombosis and potential liver toxicity in LDLR-/- mice fed with high-fat diet. Read More

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Secondary substitutions in the hemagglutinin and neuraminidase genes associated with neuraminidase inhibitor resistance are rare in the Influenza Resistance Information Study (IRIS).

Antiviral Res 2021 May 10;189:105060. Epub 2021 Mar 10.

Department of Viroscience, Erasmus Medical Center, Rotterdam, 3015GE, the Netherlands; Department of Pediatrics, Subdivision Infectious Diseases and Immunology, Erasmus Medical Center - Sophia, Rotterdam, the Netherlands. Electronic address:

Amino acid substitutions in influenza virus neuraminidase (NA) that cause resistance to neuraminidase inhibitors (NAI) generally result in virus attenuation. However, influenza viruses may acquire secondary substitutions in the NA and hemagglutinin (HA) proteins that can restore viral fitness. To assess to which extent this happens, the emergence of NAI resistance substitutions and secondary - potentially compensatory - substitutions was quantified in influenza viruses of immunocompetent individuals included in the Influenza Resistance Information Study (IRIS; NCT00884117). Read More

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Predicted occurrence, ecotoxicological risk and environmentally acquired resistance of antiviral drugs associated with COVID-19 in environmental waters.

Sci Total Environ 2021 Jul 15;776:145740. Epub 2021 Feb 15.

Discipline of Earth Science, Indian Institute of Technology Gandhinagar, Gujarat 382 355, India.

Antiviral drugs have been used to treat the ever-growing number of coronavirus disease, 2019 (COVID-19) patients. Consequently, unprecedented amounts of such drug residues discharging into ambient waters raise concerns on the potential ecotoxicological effects to aquatic lives, as well as development of antiviral drug-resistance in wildlife. Here, we estimated the occurrence, fate and ecotoxicological risk of 11 therapeutic agents suggested as drugs for COVID-19 treatment and their 13 metabolites in wastewater and environmental waters, based on drug consumption, physical-chemical property, and ecotoxicological and pharmacological data for the drugs, with the aid of quantitative structure-activity relationship (QSAR) modelling. Read More

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Infliximab and Intravenous Gammaglobulin in Hospitalized Severe COVID-19 Patients in Intensive Care Unit.

Arch Iran Med 2021 Feb 1;24(2):139-143. Epub 2021 Feb 1.

Department of Internal Medicine, Firoozgar Medical and Educational Hospital, Iran University of Medical Sciences, Tehran, Iran.

Background: Severe coronavirus disease 2019 (COVID-19) may lead to the cytokine storm syndrome which may cause acute respiratory failure syndrome and death. Our aim was to investigate the therapeutic effects of infliximab, intravenous gammaglobulin (IVIg) or combination therapy in patients with severe COVID-19 disease admitted to the intensive care unit (ICU).

Methods: In this observational research, we studied 104 intubated adult patients with severe COVID-19 infection (based on clinical symptoms, and radiographic or CT scan parameters) who were admitted to the ICU of a multispecialty hospital during March 2020 in Tehran, Iran. Read More

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February 2021

Investigation of genetic variation: Neuraminidase gene of influenza A virus H1N1/pdm09, Shiraz, Iran (2015-2016).

J Med Virol 2021 Feb 19. Epub 2021 Feb 19.

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

Oseltamivir and antiviral agents are frequently used for the prevention and treatment of influenza infection. However, resistance to oseltamivir has been reported globally due to a mutation in the Influenza virus neuraminidase gene. Such resistance will be detected by genotyping and phenotyping studies of viral isolates. Read More

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February 2021

Expanded table: Antiviral drugs for influenza.

Authors:

Med Lett Drugs Ther 2020 11 2;62(1610):e2-e4. Epub 2020 Nov 2.

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November 2020

Antiviral drugs for influenza for 2020-2021.

Authors:

Med Lett Drugs Ther 2020 11;62(1610):169-172

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November 2020

Effects of Different Drug Combinations in Immunodeficient Mice Infected with an Influenza A/H3N2 Virus.

Microorganisms 2020 Dec 11;8(12). Epub 2020 Dec 11.

Research Center in Infectious Diseases of the CHU of Québec, Laval University, Québec City, QC G1V 4G2, Canada.

The prolonged treatment of immunosuppressed (IS) individuals with anti-influenza monotherapies may lead to the emergence of drug-resistant variants. Herein, we evaluated oseltamivir and polymerase inhibitors combinations against influenza A/H3N2 infections in an IS mouse model. Mice were IS with cyclophosphamide and infected with 3 × 10 PFU of a mouse-adapted A/Switzerland/9715293/2013 (H3N2) virus. Read More

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December 2020

Baloxavir treatment of oseltamivir-resistant influenza A/H1pdm09 in two immunocompromised patients.

Transpl Infect Dis 2020 Dec 5:e13542. Epub 2020 Dec 5.

Laboratory of Viral Diseases, Wadsworth Center, New York State Department of Health, Albany, NY, USA.

Few treatment options are available for oseltamivir-resistant influenza. It has been proposed that baloxavir can be effective in this setting due to its distinct mechanism of action but clinical experience is lacking for immunocompromised patients. We report two such cases treated with baloxavir after failure of oseltamivir and detection of oseltamivir resistance mutations. Read More

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December 2020

Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia.

Pharmaceutics 2020 Nov 27;12(12). Epub 2020 Nov 27.

Deva Holding A.S., Istanbul 34303, Turkey.

Oseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment of influenza and as a potential treatment option when in combination with other medication in the fight against the corona virus disease (COVID-19) pneumonia. In this study, OP was formulated as a dry powder for inhalation, which allows drug targeting to the site of action and potentially reduces the dose, aiming a more efficient therapy. Binary formulations were based on micronized excipient particles acting like diluents, which were blended with the drug OP. Read More

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November 2020

Genetic sequencing of influenza A (H1N1) pdm09 isolates from South India, collected between 2011 and 2015 to detect mutations affecting virulence and resistance to oseltamivir.

Indian J Med Microbiol 2020 Jul-Dec;38(3 & 4):324-337

Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

Background: Influenza A viruses evolve continuously and the two surface antigens, hemagglutinin (HA) and neuraminidase (NA) have been the target proteins for research as they are vital components in determining the virulence, immune effectiveness, pathogenicity, transmission and resistance.

Methods: Both HA and NA (partial genes) of 45 pandemic influenza A(H1N1)pdm09 isolates were sequenced. Phylogenetic analysis was performed with reference to representative global isolates retrieved from Influenza Virus Resource (IVR), GISAID EpiFluTM and GenBank and evolutionary analyses. Read More

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November 2020

Profiling of Laninamivir-Resistant Substitutions in N3 to N9 Avian Influenza Virus Neuraminidase Subtypes and Their Association with Susceptibility.

J Virol 2020 12 9;95(1). Epub 2020 Dec 9.

Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea

Laninamivir (LAN) is a long-acting neuraminidase (NA) inhibitor (NAI) with a similar binding profile in the influenza NA enzyme active site as those of other NAIs, oseltamivir (OS), zanamivir (ZAN), and peramivir, and may share common resistance markers with these NAIs. We screened viruses with NA substitutions previously found during OS and ZAN selection in avian influenza viruses (AIVs) of the N3 to N9 subtypes for LAN susceptibility. Of the 72 NA substitutions, 19 conferred resistance to LAN, which ranged from 11. Read More

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December 2020

In Vitro Combinations of Baloxavir Acid and Other Inhibitors against Seasonal Influenza A Viruses.

Viruses 2020 10 8;12(10). Epub 2020 Oct 8.

Centre Hospitalier Universitaire de Québec-Centre Hospitalier de l'Université Laval (CHUQ-CHUL) and Laval University, Québec City, QC G1V 4G2, Canada.

Two antiviral classes, the neuraminidase inhibitors (NAIs) and polymerase inhibitors (baloxavir marboxil and favipiravir) can be used to prevent and treat influenza infections during seasonal epidemics and pandemics. However, prolonged treatment may lead to the emergence of drug resistance. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Read More

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October 2020

Intravenous Zanamivir: A Viable Option for Critically Ill Patients With Influenza.

Authors:
Douglas Slain

Ann Pharmacother 2021 Jun 5;55(6):760-771. Epub 2020 Oct 5.

West Virginia University, Morgantown, WV, USA.

Objective: To review the pharmacology, clinical trial data, and clinical implications for the intravenous formulation of zanamivir.

Data Sources: MEDLINE, PubMed, EMBASE, and Google Scholar were searched during November 2019 to July 2020. Search terms and were used. Read More

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Fitness of influenza A and B viruses with reduced susceptibility to baloxavir: A mini-review.

Rev Med Virol 2021 May 25;31(3):e2175. Epub 2020 Sep 25.

CHUQ-CHUL and Laval University, Québec, Canada.

Neuraminidase inhibitors (NAIs), that currently include oseltamivir (Tamiflu ), zanamivir (Relenza ), peramivir (Rapivab ) and laninamivir (Inavir ), constitute an important class of antivirals recommended against seasonal influenza A and B infections. NAIs target the surface NA protein whose sialidase activity is responsible for virion release from infected cells. Because of their pivotal role in the transcription/translation process, the polymerase acidic (PA) and polymerase basic 1 and 2 (PB1 and PB2, respectively) internal proteins also constitute targets of interest for the development of additional anti-influenza agents. Read More

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In Vitro Characterization of Multidrug-Resistant Influenza A(H1N1)pdm09 Viruses Carrying a Dual Neuraminidase Mutation Isolated from Immunocompromised Patients.

Pathogens 2020 Sep 2;9(9). Epub 2020 Sep 2.

Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.

Influenza A(H1N1)pdm09 viruses carrying a dual neuraminidase (NA) substitution were isolated from immunocompromised patients after administration of one or more NA inhibitors. These mutant viruses possessed an H275Y/I223R, H275Y/I223K, or H275Y/G147R substitution in their NA and showed enhanced cross-resistance to oseltamivir and peramivir and reduced susceptibility to zanamivir compared to single H275Y mutant viruses. Baloxavir could be a treatment option against the multidrug-resistant viruses because these dual H275Y mutant viruses showed susceptibility to this drug. Read More

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September 2020

Profile and generation of reduced neuraminidase inhibitor susceptibility in highly pathogenic avian influenza H7N9 virus from human cases in Mainland of China, 2016-2019.

Virology 2020 10 8;549:77-84. Epub 2020 Aug 8.

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, China. Electronic address:

Human infections with highly pathogenic avian influenza (HPAI) H7N9 virus were detected in late 2016. We examined the drug resistance profile of 30 HPAI H7N9 isolates from Mainland of China (2016-2019). Altogether, 23% (7/30) carried neuraminidase inhibitors (NAIs) - resistance mutations, and 13% (4/30) displayed reduced susceptibility to NAIs in neuraminidase (NA) inhibition test. Read More

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October 2020

Pharmacologic effects of oseltamivir in immunocompromised adult patients as assessed by population PK/PD analysis and drug-disease modelling for dosing regimen optimization.

Br J Clin Pharmacol 2021 Mar 9;87(3):1359-1368. Epub 2020 Sep 9.

Roche Innovation Center New York, Roche Pharmaceutical Research and Early Development, New York, NY, USA.

Aim: Pharmacologic effects were analysed to determine a dose recommendation for oseltamivir in immunocompromised (IC) adults with influenza.

Methods: Quantitative clinical pharmacology methods were applied to data from 160 adult IC patients (aged 18-78 years) from two studies (NV20234, 150 patients; NV25118, 10 patients) who received oseltamivir 75-200 mg twice daily for up to 10 days. An established population-pharmacokinetic (PK) model with additional effects on oseltamivir and oseltamivir carboxylate (OC) clearance described the PK characteristics of oseltamivir in IC patients versus otherwise healthy (OwH) patients from previous clinical trials. Read More

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Substitutions at H134 and in the 430-loop region in influenza B neuraminidases can confer reduced susceptibility to multiple neuraminidase inhibitors.

Antiviral Res 2020 10 1;182:104895. Epub 2020 Aug 1.

CSIRO Manufacturing, 343 Royal Parade, Parkville, 3052, Australia. Electronic address:

With the introduction of the influenza specific neuraminidase inhibitors (NAIs) in 1999, there were concerns about the emergence and spread of resistant viruses in the community setting. Surveillance and testing of community isolates for their susceptibility to the NAIs was initially carried out by the Neuraminidase Inhibitor Susceptibility Network (NISN) and has subsequently been taken on by the global WHO influenza network laboratories. During the NISN surveillance, we identified two Yamagata lineage influenza B viruses with amino acid substitutions of H134Y (B/Auckland/2/2001) or W438R (B/Yokohama/12/2005) which had slightly elevated IC values for zanamivir and/or oseltamivir, but not sufficiently to be characterized as mild outliers at the time. Read More

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October 2020

Functional neuraminidase inhibitor resistance motifs in avian influenza A(H5Nx) viruses.

Antiviral Res 2020 10 1;182:104886. Epub 2020 Aug 1.

The Pirbright Institute, Pirbright, United Kingdom. Electronic address:

Neuraminidase inhibitors (NAIs) are antiviral agents recommended worldwide to treat or prevent influenza virus infections in humans. Past influenza virus pandemics seeded by zoonotic infection by avian influenza viruses (AIV) as well as the increasing number of human infections with AIV have shown the importance of having information about resistance to NAIs by avian NAs that could cross the species barrier. In this study we introduced four NAI resistance-associated mutations (N2 numbering) previously found in human infections into the NA of three current AIV subtypes of the H5Nx genotype that threaten the poultry industry and human health: highly pathogenic H5N8, H5N6 and H5N2. Read More

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October 2020

Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity.

Viruses 2020 07 24;12(8). Epub 2020 Jul 24.

IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, España.

Oseltamivir is a common therapy against influenza A virus (IAV) infections. The acquisition of oseltamivir resistance (OR) mutations, such as H275Y, hampers viral fitness. However, OR H1N1 viruses have demonstrated the ability to spread throughout different populations. Read More

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Characterization of neuraminidase inhibitor-resistant influenza virus isolates from immunocompromised patients in the Republic of Korea.

Virol J 2020 07 6;17(1):94. Epub 2020 Jul 6.

Division of Viral Diseases, Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Cheongju-si, South Korea.

Background: The emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemics of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission.

Methods: Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018-2019 season. Read More

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Successful treatment with baloxavir marboxil of a patient with peramivir-resistant influenza A/H3N2 with a dual E119D/R292K substitution after allogeneic hematopoietic cell transplantation: a case report.

BMC Infect Dis 2020 Jul 6;20(1):478. Epub 2020 Jul 6.

Department of Infection Control Science, Graduate School of Medicine, Osaka City University, Osaka, Japan.

Background: Extended use of oseltamivir in an immunocompromised host could reportedly induce neuraminidase gene mutation possibly leading to oseltamivir-resistant influenza A/H3N2 virus. To our knowledge, no report is available on the clinical course of a severely immunocompromised patient with a dual E119D/R292K neuraminidase mutated-influenza A/H3N2 during the administration of peramivir.

Case Presentation: A 49-year-old male patient was admitted for second allogeneic hematopoietic cell transplantation for active acute leukemia. Read More

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Combinatory Treatment with Oseltamivir and Itraconazole Targeting Both Virus and Host Factors in Influenza A Virus Infection.

Viruses 2020 06 29;12(7). Epub 2020 Jun 29.

Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation and "Cells in Motion" Interfaculty Centre, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany.

Influenza virus infections and their associated morbidity and mortality are a major threat to global health. Vaccination is an effective influenza prevention measure; however, the effectiveness is challenged by the rapid changes in the influenza virus genome leading to viral adaptation. Emerging viral resistance to the neuraminidase inhibitor oseltamivir limits the treatment of acute influenza infections. Read More

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A retrospective observational study of the treatment of a nosocomial infection caused by oseltamivir-resistant influenza virus A with baloxavir marboxil.

Respir Investig 2020 Sep 27;58(5):403-408. Epub 2020 Jun 27.

Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. Electronic address:

Background: Nosocomial (hospital-acquired) influenza A virus infection is a very important clinical issue. The objective of this study is to describe the effect of baloxavir marboxil in controlling an outbreak of this infection.

Methods: A retrospective observational study was performed to assess the effectiveness of baloxavir marboxil in the treatment of nosocomial infections caused by oseltamivir-resistant influenza virus A. Read More

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September 2020