And the third winner of the Merit Prize in the CoS Science Communication Writing Competition, Devika Menon from the School of Biological Sciences! She wrote about “L-P Polymerase Inhibitors- The Possible Doom Of Pneumonia.” Congratulations, Devika!
L-P Polymerase Inhibitors- The Possible Doom Of Pneumonia
Written by Devika Menon
One hundred and fifty million cases reported in a year.
A mortality rate of thirty percent.
The number two cause of death in Singapore.
Pneumonia affects babies, infants and elderly – the age groups with the weakest immune system and is primarily caused by bacterial or viral infections. Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viruses that can cause pneumonia. RSV is transferred when people touch their eyes or nose after having directly touched contaminated objects. HMPV is transferred from the saliva, cough or sneeze of an infected person.
Currently there are no vaccines or treatments for pneumonia caused by HMPV and RSV. However, recent research from NTU scientists have revealed a clue to hack the mechanism of this deadly disease. Once the virus enters the respiratory system, it makes its way into the cells that line our windpipe (epithelial cells). Inside epithelial cells, viral replication begins i.e the virus makes multiple copies of itself in order to spread the infection. The process is a red alert for our immune system which immediately dispatches lymphocytes (white blood cells that defend us against bacteria and viruses that enter our body) to our rescue. The white blood cells generate inflammation in our respiratory system in order to expel the virus. In an attempt to destroy the virus, the inflammation damages our respiratory system as well as generating symptoms like chest pain, dry cough and difficulty in breathing.
In essence, the whole process is lot like an alien invading our territory. Except, in an attempt to drive them away, we end up poisoning our own planet. However, it isn’t so simple. There are nitty-gritty details in the process that enables this alien invader a.k.a the virus to propagate the infection. In order to trick the human cells into allowing virus replication, it releases certain proteins. These proteins interact with other proteins to form a larger group of associated proteins – a protein complex. Protein complexes like L-P polymerase released by HMPV enables viral replication. This polymerase is involved in making duplicate copies of the viral genetic material so that the virus can replicate.
Dr.Julien Lescar and his team of scientists from School of Biological Sciences at NTU, used cryo-electron microscopy to deduce the structure of the L-P polymerase. In the process, a beam of electrons is passed through a frozen protein solution. Electrons bump into the protein and get scattered. As they leave the solution, they create a high resolution, magnified image of the protein structure. The team of scientists at NTU developed the three-dimensional computerized model of the L-P polymerase using this method. This model developed by the team allows visualization and identification of specific regions on the complex that interact with other proteins to perform its function (which is to enable replication).
Hence, it opens a new possibility of developing drugs against pneumonia that are inhibitors- substances that block the function of an enzyme- in this case, of L-P polymerase. Inhibitors are substances that can bind to regions on the enzyme, blocking its function. Hence, inhibitors of L-P Polymerase could have the ability to prevent virus replication. If such drugs are discovered, viral replication and progressive infection could thus be prevented. What is even more exciting is that such inhibitors could have the potential to treat several other respiratory diseases in the future.