introduction: influenza is a contagious acute viral disease of the respiratory tract that causes fever, headache, muscle aches and cough. one of the unique features of influenza virus is antigenic variation in viral protein neuraminidase (na) which causes emergence of new virus variants. na is responsible for the release and spread of progeny virions. due to the continuous changes of na genes, ...

Drugs inhibiting the influenza A virus (IAV) neuraminidase (NA) are the cornerstone of anti-IAV chemotherapy and prophylaxis in man. Drug-resistant mutations in NA arise frequently in human isolates, limiting the therapeutic application of NA inhibitors. Here, we show that antibody-driven antigenic variation in one domain of the H1 hemagglutinin Sa site leads to compensatory mutations in NA, re...

Neuraminidase (NA) inhibitors are used for the prevention and treatment of influenza A virus infections. Two subtypes of NA, N1 and N2, predominate in viruses that infect humans, but differential patterns of drug resistance have emerged in each subtype despite highly homologous active sites. To understand the molecular basis for the selection of these drug resistance mutations, structural and d...

The development of drug resistance is a major drawback to any antiviral therapy, and the specific anti-influenza drugs, the neuraminidase (NA) inhibitors (NAIs), are not excluded from this rule. The impact of drug resistance depends on the degree of reduction in fitness of the particular drug-resistant virus. If the resistance mutations lead to only a modest biological fitness cost and the viru...

The therapeutic benefits of the neuraminidase (NA) inhibitor oseltamivir are dampened by the emergence of drug resistance mutations in influenza A virus (IAV). To investigate the mechanistic features that underlie resistance, we developed an approach to quantify the effects of all possible single-nucleotide substitutions introduced into important regions of NA. We determined the experimental fi...

Nucleotide or nucleoside analog (NA) drug resistance has increasingly become a problem in HBV treatment. Due to the similarity between HBV polymerase and HIV-1 reverse transcriptase, knowledge obtained from HIV research might be applied to the treatment of HBV infection. A previous study has shown that HIV-1 ribonuclease H (RNase H) mutation may contribute to nucleoside reverse transcriptase in...

The M2 blockers amantadine and rimantadine and the neuraminidase (NA) inhibitors (NAIs) oseltamivir and zanamivir are approved by the FDA for use for the control of influenza A virus infections. The 2009 pandemic influenza A (H1N1) viruses (H1N1pdm) are reassortants that acquired M and NA gene segments from a Eurasian adamantane-resistant swine influenza virus. NAI resistance in the H1N1pdm vir...

OBJECTIVES To monitor antiviral drug resistance among seasonal influenza viruses isolated in Korea during the 2008-2009 influenza season, we examined influenza isolates collected through Korea Influenza Surveillance Scheme for antiviral drug susceptibility. METHODS For genetic analysis of antiviral drug resistance, the matrix (M2) and neuraminidase (NA) genes of each isolate were amplified by...

Quantitatively predicting changes in drug sensitivity associated with residue mutations is a major challenge in structural biology. By expanding the limits of free energy calculations, we successfully identified mutations in influenza neuraminidase (NA) that confer drug resistance to two antiviral drugs, zanamivir and oseltamivir. We augmented molecular dynamics (MD) with Hamiltonian Replica Ex...

Infection with influenza virus is a major public health problem, causing serious illness and death each year. Emergence of drug-resistant influenza virus strains limits the effectiveness of drug treatment. Importantly, a dual H275Y/I223R mutation detected in the pandemic influenza A 2009 virus strain results in multidrug resistance to current neuraminidase (NA) drugs. Therefore, discovery of ne...