Search results for: neuraminidase

Authors: J. Tengrang, T. Rungrotmongkol, S. Hannongbua

Abstract:

Every 2-3 years the influenza B virus serves epidemics. Neuraminidase (NA) is an important target for influenza drug design. Although, oseltamivir, an oral neuraminidase drug, has been shown good inhibitory efficiency against wild-type of influenza B virus, the lower susceptibility to the R152K mutation has been reported. Better understanding of oseltamivir efficiency and resistance toward the influenza B NA wild-type and R152K mutant, respectively, could be useful for rational drug design. Here, two complex systems of wild-type and R152K NAs with oseltamivir bound were studied using molecular dynamics (MD) simulations. Based on 5-ns MD simulation, the loss of notable hydrogen bond and decrease in per-residue decomposition energy from the mutated residue K152 contributed to drug compared to those of R152 in wildtype were found to be a primary source of high-level of oseltamivir resistance due to the R152K mutation.

Keywords: Influenza B neuraminidase, Molecular dynamics simulation, Oseltamivir resistance, R152K mutant

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Authors: Aditi Shukla, Ambarish S. Vidyarthi, Subir Samanta

Abstract:

The worldwide prevalence of H3N2 influenza virus and its increasing resistance to the existing drugs necessitates for the development of an improved/better targeting anti-influenza drug. H3N2 influenza neuraminidase is one of the two membrane-bound proteins belonging to group-2 neuraminidases. It acts as key player involved in viral pathogenicity and hence, is an important target of anti-influenza drugs. Oseltamivir is one of the potent drugs targeting this neuraminidase. In the present work, we have taken subtype N2 neuraminidase as the receptor and probable analogs of oseltamivir as drug molecules to study the protein-drug interaction in anticipation of finding efficient modified candidate compound. Oseltamivir analogs were made by modifying the functional groups using Marvin Sketch software and were docked using Schrodinger-s Glide. Oseltamivir analog 10 was detected to have significant energy value (16% less compared to Oseltamivir) and could be the probable lead molecule. It infers that some of the modified compounds can interact in a novel manner with increased hydrogen bonding at the active site of neuraminidase and it might be better than the original drug. Further work can be carried out such as enzymatic inhibition studies; synthesis and crystallizing the drug-target complex to analyze the interactions biologically.

Keywords: H3N2 Influenza, Neuraminidase, Oseltamiviranalogs, structure based drug designing

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Authors: Robles F, Uribe A, Guadarrama A , Castellanos L, González C.

Abstract:

The main objective of this study was to demonstrate that differentiation of infected and vaccinated animals (DIVA) strategy using different ELISA tests is possible when a subunit vaccine (Haemagglutinin protein) is used to prevent Avian influenza. Special emphasis was placed on the differentiation in the serological response to different components of the AIV (Nucleoprotein, Neuraminidase, Haemagglutinin, Nucleocapsid) between chickens that were vaccinated with a whole virus kill vaccine and recombinant vaccine. Furthermore, the potential use of this DIVA strategy using ELISA assays to detect Neuraminidase 1 (N1) was analyzed as strategy in countries where the field virus is H5N1 and the vaccine used is formulated with H5N2. Detection of AIV-s antibodies to any component in serum was negative for all animals on the study days 0-13. At study day 14 the titers of antibodies against Nucleoprotein (NP) and Nucleocapsid (NC) rose in the experimental groups vaccinated with Volvac® AI KV and were negatives during all the trial in the experimental groups vaccinated with a subunit H5; significant statistically differences were observed between these groups (p < 0.05). The seroconversion either Haemagglutinin or Neuraminidase was evident after 21 days post-vaccination in the experimental groups vaccinated with the respective viral fraction. Regarding the main aim of this study and according with the results that were obtained, use a combination of different ELISA test as a DIVA strategy is feasible when the vaccination is carry out with a subunit H5 vaccine. Also is possible to use the ELISA kit to detect Neuraminidase (either N1 or N2) as a DIVA concept in countries where H5N1 is present and the vaccination programs are done with H5N2 vaccine.

Keywords: Avian Influenza Virus, "DIVA concept", ELISAassay, subunit H5 vaccine.

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Authors: A. Meeprasert, W. Khuntawee, S. Hannongbua, T. Rungrotmongkol

Abstract:

Viral influenza A subtypes H5N1 and pandemic H1N1 (pH1N1) have worldwide emerged and transmitted. The most common anti-influenza drug for treatment of both seasonal and pandemic influenza viruses is oseltamivir that nowadays becomes resistance to influenza neuraminidase. The novel long-acting drug, laninamivir, was discovered for treatment of the patients infected with influenza B and influenza A viruses. In the present study, laninamivir complexed with wild-type strain of both H5N1 and pH1N1 viruses were comparatively determined the structures and drug-target interactions by means of molecular dynamics (MD) simulations. The results show that the hydrogen bonding interactions formed between laninamivir and its binding residues are likely similar for the two systems. Additionally, the presence of intermolecular interactions from laninamivir to the residues in the binding pocket is established through their side chains in accordance with hydrogen bond interactions.

Keywords: Laninamivir, neuraminidase, H5N1, pandemic H1N1, wild-type, MD simulation

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Authors: Patsaraporn Somboonsak, Mud-Armeen Munlin

Abstract:

In April 2009, a new variant of Influenza A virus subtype H1N1 emerged in Mexico and spread all over the world. The influenza has three subtypes in human (H1N1, H1N2 and H3N2) Types B and C influenza tend to be associated with local or regional epidemics. Preliminary genetic characterization of the influenza viruses has identified them as swine influenza A (H1N1) viruses. Nucleotide sequence analysis of the Haemagglutinin (HA) and Neuraminidase (NA) are similar to each other and the majority of their genes of swine influenza viruses, two genes coding for the neuraminidase (NA) and matrix (M) proteins are similar to corresponding genes of swine influenza. Sequence similarity between the 2009 A (H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Nucleic acid sequence Maximum Likelihood (MCL) and DNA Empirical base frequencies, Phylogenetic relationship amongst the HA genes of H1N1 virus isolated in Genbank having high nucleotide sequence homology. In this paper we used 16 HA nucleotide sequences from NCBI for computing sequence relationships similarity of swine influenza A virus using the following method MCL the result is 28%, 36.64% for Optimal tree with the sum of branch length, 35.62% for Interior branch phylogeny Neighber – Join Tree, 1.85% for the overall transition/transversion, and 8.28% for Overall mean distance.

Keywords: Sequence DNA, Relationship of swine, Swineinfluenza, Sequence Similarity

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