How to Conquer Tamiflu Influenza Virus
The virus, a parasite living
beings, are also constantly by mutating in order to trick the host cell's
defense system. This method allows the virus to enter the cell and makes the
virus can escape from the attack of the host cell. The virus could then
multiply within the host cells and can lead to death of the infected organism.
Not only that, by mutating, the virus can become resistant to the drugs used to
suppress human virus.
One of the viruses that are
harmful to humans are influenza virus. In the last five years the world
community shocked by the spread of one subtype of influenza A, which is called
the H5N1 bird flu. The virus is reported to have killed 262 people worldwide.
In Indonesia alone victims reached 115 people.
Unfinished face of H5N1, now the
world community was shocked by the spread of infection and transmission of
influenza A virus subtype H1N1. In a relatively short time, the virus has
killed more than 400 people worldwide. The world was declared in a state of
pandemic influenza.
On fears the pandemic, reported
that it started there influenza virus, both H5N1 and H1N1, which is resistant
to Tamiflu. In fact, the mainstay antiviral drug Tamiflu used to counteract the
spread of H5N1 or H1N1.
Inhibition "neuraminidase"
Oseltamivir, influenza antiviral
drug known as Tamiflu, works by inhibiting neuraminidase, which is a protein
enzyme present on the surface of the virus. In inhibiting neuraminidase,
oseltamivir attaches to the enzyme active site so that the neuraminidase enzyme
becomes inactive. Neuraminidase instrumental in releasing the new virus is
formed so that this new virus can spread and infect other cells.
Virus newly formed as a result of
proliferation in cells initially still attached to the cell surface via sialic
acid residues. To release the virus from the host cell membrane, neuraminidase
cut the sialic acid residues. If the neuraminidase activity is inhibited by
oseltamivir, the newly formed virus cannot escape to spread so that the
proliferation of the virus can be stopped.
This condition will help the
immune system to win the battle against the influenza virus was attacking so
that an infected person can recover.
However, if oseltamivir fails to
inhibit the activity of neuraminidase, the virus will continue to multiply and
can spread from one cell to another cell, although patients given the drug
Tamiflu. This situation is very dangerous and can threaten the lives of patients.
For example, cases of patient deaths due to H5N1 resistant to Tamiflu, among
others, have been reported in Vietnam and the consequences of Tamiflu-resistant
H1N1 infection have been reported in the Netherlands.
Gene mutation "neuraminidase"
The influenza virus can become
resistant to Tamiflu because of a mutation in the neuraminidase gene, the gene
coding for the protein neuraminidase. Mutations are changes in the nucleotide
bases in a DNA molecule or gene, for example, changes in the base cytosine (C)
into the base thymine (T). These base changes lead to changes in the genetic
code that could further alter the amino acid residues of the proteins encoded.
Neuraminidase genes measuring
1,362 base pairs and encodes a protein neuraminidase, which consists of 454
amino acid residues. C to T mutation at nucleotide bases 763 to change the
amino acid residues at all 454 of the neuraminidase protein histidine to
tyrosine.
These changes resulted in
oseltamivir attachment points on neuraminidase protein changes so that
oseltamivir can no longer be bound to the neuraminidase (see Figure). As a
result, could not be inhibited neuraminidase activity and viral replication
cannot be stopped by Tamiflu. Other mutations were also reported to cause
resistance to Tamiflu is a mutation that changed amino acid residue 292 from
arginine to lysine and transform into the residue to 294 from asparagine into
serine.
To anticipate the emergence of a
dangerous mutation in the influenza virus, sequences or the nucleotide sequences
of DNA virus that is endemic need to be analyzed regularly. Neuraminidase gene
changes need to be monitored to anticipate the outbreak of the virus resistant
to Tamiflu. In addition, influenza antiviral drug alternatives should be
developed. Treatment using several compounds with different ways of working
should also be considered.