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 Q4 / 2016

Antiviral resistance

The I427T neuraminidase (NA) substitution located outside the NA active site of an influenza A(H1N1) pdm09 variant with reduced susceptibility to NA inhibitors alters NA properties and impairs viral fitness

Using recombinant viruses, the I427T mutation in the neuraminidase of influenza A(H1N1)pdm09 was found to confer resistance to oseltamivir, zanamivir, peramivir and laninamivir. However, in vitro and in vivo replication studies of the variant revealed a compromised viral fitness…read more

Biological fitness and natural selection of amantadine resistant variants of avian influenza H5N1 viruses

Using recombinant viruses, amantadine resistance mutation, S31N, of the M2 protein in avian influenza A(H5N1) virus was found to be genetically stable with the S31N variants having a higher replication fitness compared to wild-type viruses in vitro…read more

Investigational antivirals

Antiviral efficacy of Verdinexor in vivo in two animal models of influenza A virus Infection

Verdinexor, an inhibitor blocking the nuclear export of viral ribonucleoprotein complexes, has been shown to exhibit therapeutic effectiveness in inhibiting viral replication and inflammatory immune responses in both mouse and ferret model of influenza infection… read more

Rapid control of pandemic H1N1 influenza by targeting NKT-cells

Targeting the natural killer T cells with agonist compound, α-GalCer in the swine (piglet) model of influenza infection can ameliorated disease symptoms, reduce viral replication in both the upper and lower respiratory tracts and prevent infection associated lung pathology. Improvement in symptoms were only observed when the α-GalCer was administered intranasally …read more


Review articles

Anti-influenza virus effects of catechins: A molecular and clinical review

A review on the antiviral properties of catechins, a class of polyphenolic flavonoids, against influenza infection…read more

The pharmacological management of severe influenza infection - 'existing and emerging therapies'

A review summarising the current and emerging antiviral therapies for the treatment of severe influenza infection…read more

Q3 / 2016

Antiviral resistance

The E119D neuraminidase mutation identified in a multidrug-resistant influenza A(H1N1)pdm09 isolate severely alters viral fitness in vitro and in animal models

Recombinant A(H1N1)pdm09 variant viruses with the E119D and E119D+H275Y neuraminidase mutations displayed lower in vitro and in vivo replication fitness compared to wild-type virus, and E119D mutation was genetically unstable… read more 

Competitive fitness of influenza B viruses possessing E119A and H274Y neuraminidase inhibitor resistance-associated substitutions in ferrets

Recombinant influenza B viruses with the E119A neuraminidase (NA) mutation showed reduced replication fitness whereas variant viruses with the H274Y NA mutation showed comparable replication fitness to wild-type (WT) recombinant virus. Both E119A and H274Y variants did not display replication advantage over WT recombinant viruses in ferrets… read more

Impact on antiviral resistance of E119V, I222L and R292K substitutions in influenza A viruses bearing a group 2 neuraminidase (N2, N3, N6, N7 and N9)

All group 2 neuraminidase (N2, N3, N6, N7 and N9) with the resistant neuraminidase mutations, E119V, I222L and R292K can confer reduced inhibition by oseltamivir… read more 

Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir

Using a cell based screening assay, it was found that favipiravir treatment in influenza infected patients (n=57) did not result in drug resistance… read more 

Clinical reports

Pharmacokinetics of oseltamivir in infants under the age of 1 year

A prospective, uncontrolled, open label study of the pharmacokinetics of oseltamivir in influenza-infected children under 1 year of age (n=4) showed that the dose range of 2.35-3mg/kg/dose are well-tolerated and resulted in a target oseltamivir carboxylate plasma concentration in excess of the proposed 12-hour target exposure in children of this age… read more 

Investigational antivirals

Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans

Mycophenolic acid, an immunosuppressant drug, was found to have inhibitory effect on the in vitro replication of different types and subtypes of influenza viruses, such as A(H1N1)pdm09, A(H3N2), A(H7N9) and B viruses… read more 

The superiority of IFN-lambda as a therapeutic candidate to control acute influenza viral lung infection

The administration of Interferon-lamda 2/3 protein in a mouse model of influenza infection significantly reduced the replication of influenza A(H1N1) and A(H5N1) in the lungs and induced an up-regulation of interferon-stimulated genes as an innate immune responses towards the infection… read more

IFNλ is a potent anti-influenza therapeutic without the inflammatory side effects of IFNα treatment

In vitro assessment of the treatment effectiveness of interferon-lamda revealed their ability to exert an inhibitory effect on both influenza virus replication and the stimulation of immune cells, to prevent immune-mediated lung damage caused by immune-stimulating type I interferon, such as interferon-gamma… read more  

Human monoclonal antibody 81.39a effectively neutralizes emerging influenza A viruses of group 1 and 2 hemagglutinins

Human IgG1 monoclonal antibody 81.39a exerts broad neutralising activity against influenza A virus of different hemagglutinin subtypes in vitro. In vivo assessment using mice and ferret model of influenza infection showed that the monoclonal antibodies were able to protect and ameliorate disease severity of influenza infection… read more

A novel endonuclease inhibitor exhibits broad-spectrum anti-influenza virus activity in vitro

Putative inhibitor of influenza acid polymerase, RO-7, exhibits low toxicity and broad inhibitory effect on influenza A(H1N1), A(H1N1)pdm09, A(H3N2), B viruses (Yamagata and Victoria-lineages), A(H5N1), A(H7N9) and A(H9N2) in vitro… read more


Computational modelling

Oseltamivir PK/PD modelling and simulation to evaluate treatment strategies against influenza-pneumonia coinfection

Mathematical modelling of influenza-streptococcus pneumonia co-infection with oseltamivir treatment showed that the recommended treatment regimen at 75 mg, twice daily for 5 days in human may yield 47% antiviral efficacy and 9% antibacterial efficacy, and 49% antiviral efficacy and 16% antibacterial efficacy when the dose increases to 150 mg. The model suggests that decreasing oseltamivir intake to once a day or increasing dosing duration to 10 days do not improve both antiviral or antibacterial efficacy… read more

Review articles 

Current and novel antiviral strategies for influenza infection

A review summarising the landscape of currently licensed antiviral and promising investigational antiviral compounds for influenza infection… read more

Antiviral therapies on the horizon for influenza

A review on the various investigational antivirals (host cell-directed metabolic inhibitors, broad neutralising antibodies, viral polymerase inhibitors etc.) at different stages of development and/or clinical trial… read more

The influenza virus polymerase complex: an update on its structure, functions, and significance for antiviral drug design

A review on the progress in the understanding of influenza virus polymerase complex and the implication in the design of novel antiviral drugs… read more 


Q2 / 2016

Antiviral resistance

Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor

Using direct mutagenesis to introduce point mutations in the endonuclease domains, four mutations (T20A, I79L, F105S, and E119D) conferring resistance to endonuclease inhibitor, L-74200, were identified…read more

Clinical reports

Rising oseltamivir use among hospitalized children in a post pandemic era

A high percentage of paediatrics inpatients (82%) with PCR-confirmed influenza were treated with oseltamivir in Children’s Hospital Colorado, USA from 2010 to 2014…read more

A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma

A phase I clinical trial of patients with underlying reactive airway disease reported that the usage of antiviral drug, DAS181 can increase the association of respiratory events (dyspnea, dry cough, chest discomfort etc.) following more

Host antiviral immunity

Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease

In mice model of influenza infection, it was elucidated that the increased susceptibility to influenza infection in a situation of weakened antiviral immunity is due to an elevated bacterial burden, caspase-1/11 and neutrophils-mediated tissue damage rather than viral load or MyD88-dependent signalling pathway…read more 

Investigational antivirals

Direct administration in the respiratory tract improves efficacy of broadly neutralizing anti-influenza virus monoclonal antibodies

Broadly neutralizing anti-hemagglutinin stalk monoclonal antibodies when administered intranasally or via aerosol in a mouse model of influenza infection were more effective in reducing disease associated mortality compared to systemic administration …read more 


Dual Acting Neuraminidase Inhibitors Open New Opportunities to Disrupt the Lethal Synergism between Streptococcus pneumoniae and Influenza Virus

The neuraminidases (NanA and NanB) of Streptococcus Pneumoniae were able to support influenza viral replication and the activity of this bacterial neuraminidase can be inhibited by selected neuraminidase inhibitors such as oseltamivir, DANA, katsumadain A and artocarpin…read more   


Selection of Therapeutic H5N1 Monoclonal Antibodies Following IgVH Repertoire Analysis in Mice

The screening of IgVH repertoires of mice immunized with recombinant H5N1 hemagglutinin by next generation sequencing identified two monoclonal antibodies (from an initial 35 IgVH genes) which have therapeutic and prophylactic activity in a mouse model of influenza infection…read more

Hemagglutinin-targeting Artificial MicroRNAs Expressed by Adenovirus Protect Mice From Different Clades of H5N1 Infection

Artificial microRNA (HA-1405) against hemagglutinin gene of H5N1 virus reduces replication of H5N1 viruses in vitro. The administration of HA-1405 reduces clinical symptoms and viral load in mice challenged with different H5N1 clades….read more 

Computational modelling

Impact of the H275Y and I223V Mutations in the Neuraminidase of the 2009 Pandemic Influenza Virus In Vitro and Evaluating Experimental Reproducibility

Mathematical modelling technique were used to compare the replication fitness of influenza A(H1N1)pdm09 with H275Y or I223V NA mutations to their wild-type counterpart. The modelling data suggest I223V mutants has reduced fitness compared to virus with or without H275Y NA mutation…read more

Review articles

The host immune response in respiratory virus infection: balancing virus clearance and immunopathology

A review highlighting the double-edge nature of the host immune system in response to a viral infection …read more

Oseltamivir Treatment for Children with Influenza-Like Illness in China: A Cost-Effectiveness Analysis

A cost effective analysis of the prescription of oseltamivir to children with influenza –like illness (ILI) in China revealed that empiric oseltamivir treatment in children with ILI is the most cost effective compared to treatment after post-rapid influenza diagnostic test or no treatment…read more 

Conference report

4th ISIRV antiviral group conference: 

Novel antiviral therapies for influenza and other respiratory viruses

A report summarising the 4th International Society for Influenza and other Respiratory Virus Disease (ISIRV) antiviral group conference… read more


Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza

An article written by A/Prof Aeron Hurt and Prof. Heath Kelly on the ongoing debate surrounding the use of oseltamivir for influenza…read more

Q1 / 2016

Antiviral resistance 

Detection of rare drug resistance mutations by digital PCR in a human influenza A virus
model system and clinical samples

Digital PCR demonstrates a higher sensitivity for detecting single nucleotide polymorphisms (SNPs) that correspond to
drug-resistance compared to quantitative PCR …read more

The project to standardize the drug susceptibility assay for influenza was carried out by members of the Molecular Epidemiology
Team, Influenza Division, and U.S. Centers for Disease Control and Prevention, Atlanta, GA, in collaboration with the Association
for Public Health Laboratories... read more

Clinical reports

Outcomes of influenza infections in hematopoietic cell transplant recipients: Application of an
immunodeficiency scoring index

Early administration of influenza antivirals was associated with a significant reduction in lower respiratory tract infection (LRI) in 
influenza infected patients undergoing hematopoietic cell transplant (HCT). This finding applies to all HCT patients with different
immunodeficiency scoring index (risk for LRI and death)…read more

Investigational antivirals 

Intranasal introduction of Fc-fused interleukin-7 provides long-lasting prophylaxis from
lethal influenza infection

IL-7-mFc given intranasally protects mice from lethal influenza A infection. The protective effect was associated with the
recruitment and residence of T cells in the lungs. The presence of these tissue-resident memory-like T cells in the lung
attenuate viral replication and promote expansion of influenza A virus-specific cytotoxic T cells which facilitate viral clearance
 …read more 

Immuno-modulating properties of saliphenylhalamide, SNS-032, obatoclax, and gemcitabine

Investigational antivirals, such as saliphenylhalamide, SNS-032, obatoclax and gemcitabine, were evaluated for their 
immunomodulatory effect in an in vitro cell culture system. Gemcitabine (which attenuates transcription and replication of viral
RNA in the nucleus of infected cells) was the only antiviral which promote activation of the innate immune responses in infected
cells and prime immune responses in non-infected cells…read more  

Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry

Quercetin (flavonoids) inhibit the replication of influenza A virus by interacting with the HA2 subunit…read more

Host antiviral immunity

The microRNA miR-45 targets host and influenza virus transcript to regulate antiviral
immunity and restrict viral replication

Host derived microRNA, miR-45, was found to exhibit dual functions (depending on the extent of infections) in the event 
of influenza infection by either targeting viral PB1 gene to reduce viral replication and/or regulating host-derived antiviral
immunity by targeting retinoic acid-inducible gene I (RIG-I)…read more 

A Computationally Designed Hemagglutinin Stem-Binding Protein Provides In Vivo
Protection from Influenza Independent of a Host Immune Response

Broadly neutralizing antibodies targeting a highly conserved region in the hemagglutinin (HA) stem protect against influenza
infection. Here, we investigate the protective efficacy of a protein (HB36.6) computationally designed to bind with high affinity
to the same region in the HA stem….read more

Review articles

Peramivir: an intravenous neuraminidase inhibitor

A review on the development process and the safety and treatment efficacy of peramivir …read more

Using the ferret as an animal model for investigating influenza antiviral effectiveness

A review discussing the current progress and challenges in using the ferret model to measure antiviral effectiveness…read more

The Hemagglutinin Stem-Binding Monoclonal Antibody VIS410 Controls Influenza 
Virus–Induced Acute Respiratory Distress Syndrome

Most cases of severe influenza are associated with pulmonary complications, such as acute respiratory distress syndrome
(ARDS), and no antiviral drugs of proven value for treating such complications are currently available. The use of monoclonal 
antibodies targeting the stem of the influenza virus surface hemagglutinin (HA), is a rapidly developing strategy for controlling
viruses of multiple HA more

Prepared by: Dr Ding Oh (WHO Collaborating Centre for Influenza, Melbourne)

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