Alberta Ingenuity & CMASTE
Case Study:
Preventing Influenza with Osteltamivir
In a human cell, you will find many organelles, each with its own structure and function.
One organelle is the plasma membrane. Its structure includes the phospholipid bilayer,
carbohydrates, cholesterol, proteins and glycoproteins (carbohydrates on protein
molecules). One function of the plasma membrane is to communicate with cells,
organisms and molecules to try to keep the cell healthy. The carbohydrates located
outside the plasma membrane are very important, not for storage, transport of energy,
or structure, but to help in communication. Cells and molecules do not use words, yet
these carbohydrates communicate to molecules that come into contact with the cell.
This communication may lead to a chemical reaction. Glycobiology defines the functions
of these sugars and determines how these functions are carried out. The core of AICCS
research is glycobiology. Researchers are not only looking at designing vaccines and
drugs but also looking for mechanisms which will lead to possibilities in the future.
Figure 1: Plasma membrane with carbohydrates, proteins, glycoproteins
Not all contact is healthy for the cell. Harmful visitors to the cell include bacteria and
viruses. They infect their hosts by binding to the surface carbohydrates of a cell. It is
difficult to develop anti-viral drugs because much of the virus life cycle depends on the
host. Drugs have been developed to inhibit the influenza virus’ ability to multiply.
Osteltamivir (Tamiflu) has received a lot of media attention for its potential to treat
influenza because of its ability to affect the virus enzyme with no affect on the host.
Tamiflu is a neuraminidase (NEU1) inhibitor that can be used to treat both Influenza A
and B. NEU1 is the enzyme found on the surface of an Influenza virus.
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The NEU1 extends, reaching over, to act as a catalyst cleaving the hemmagluttinin (HA),
a glycoprotein on the virus, from the sialic acid extension from the cell membrane. (See
Figure 2.) The free virus is now able to roam, searching for a new host to begin the
replication process again. One of the Principal Investigators at AICCS is leading a study,
which explores the role of cell-surface glycolipids (ex: sialic acid), for develop new
single- molecule and single- cell technologies.
Figure 2: Magnified view of the chemical reaction that occurs when the NEU1 initiates
the reaction to free the virus.
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When Tamiflu is present, NEU1 is capped by the inhibitors (Tamiflu) and hydrolysis will
not occur. The hydrolysis will only occur in the presence of an enzyme. The Influenza
virus cannot break free from the sialic acid. It is no longer capable of infecting other
cells.
Figure 3: The NEU1 is capped by the neuraminidase inhibitor (Tamiflu) preventing the
release of the virus.
Case Study Questions
1. What are the main components of the plasma membrane?
2. What are the functions of carbohydrate molecules?
3. Define glycobiology. Describe two applications of glycobiology research?
4. Explain why it is important to study cell surface glycolipids.
5. Describe the biggest challenge in developing anti-viral drugs?
6. Which protein on the influenza virus binds to the host cell? What is the functional
group is substituted on to the sialic acid for the virus protein?
7. The release of the virus is a hydrolysis reaction. What is a reaction that forms water
called? Write a balanced chemical reaction, showing all reactants and all products.
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