Assignment 2

In this post, we will explore a little bit of the literature about neuraminidase. I learned some fascinating facts about the structure and function of the protein and I hope you will enjoy them as well. Neuraminidase is a dangerous little protein- without it, influenza epidemics would be mere historical horror stories instead of current threats. It is a prime target for anti-influenza drugs.

Zhang, C., Y.L. Cao, W. Zhong, et al. Establishment of a cell-based 2009 H1N1 influenza neuraminidase inhibitors evaluation system. Yao Xue Xue Bao. 45(3): 383-387.

                In this article, the researchers were evaluating compounds that might inhibit neuraminidase function. They described neuraminidase as an influenza virus structural protein that cleaves the interaction between hemagglutinin and sialic acid, allowing the viral particles to be released from the cell. Hemagluttinin is the other structural protein in the influenza virus- the “H” in H1N1. Neuraminidase is, if you can believe it, the “N” in H1N1. Hemagluttinin aids in attaching the virus to the host cell. In this article, several compounds that were candidates for anti-influenza drugs were being researched for their potential to inhibit the activity of neuraminidase, preventing viral release from the host cell. This would be able to stop the virus from spreading to other cells.

Tisoncik, Jennifer, Ying Guo, Katie Cordero, et al. Identification of critical residues of influenza neuraminidase in viral particle release. Virology Journal 8(14).

                This article states that neuraminidase catalyzes the N-acetyl neuraminic acid (Neu5Ac) receptor removal, which makes the release of the viral particles from the host cell easier. Neuraminidase is essential to viral survival within the host. The researchers found several residues on the protein that were facing away from the structure of the virus, which may signal their importance to the function of the protein. It mentions that neuraminidase exists as a tetramer (meaning that it has four subunits), composed of the same subunit (shown in pictures in previous post). This subunit is the same across all types of influenza.

Takahashi, T., Y. Kurebayashi, K. Ikeya, et al. The low pH stability discovered in neuraminidase of 1918 pandemic influenza A virus enhances viral replication. PLoS One 5(12): e15556.

                The researchers of this article were hypothesizing about how the 1918 “Spanish flu” influenza A pandemic was so virulent. They found that the neuraminidase protein in this strain was stable in lower pH levels than normal strains. In this experiment, the sialidase activity of neuraminidase was unhindered by acidic conditions of pH 4.0, which most other strains do not tolerate.  They deleted a threonine residue at position 435 and a glycine residue at position 455 eliminated this ability to remain stable in acidic conditions. The researchers concluded that this is why the 1918 pandemic influenza virus was able to replicate so efficiently within its host.

Do you see what I mean? Neuraminidase is scary, but really cool! And because it can mutate so quickly (why there are different types of influenzas), it can adapt to all sorts of new environments... such as your body. Yikes!