Download D.5 Antiviral Medications

Antiviral Medications
What is a Virus?
• A virus is a small infectious agent.
• Viruses contain only two main components, protein and nucleic acid (either
RNA or DNA).
What is a Virus?
• Viruses have no cellular structure and are only capable of reproducing inside the
cells of other living cells. They take over the cell of a living organism, called a
host cell, and use it to carry out their own reproduction.
• The host cell’s components are used in the assembly of new viral particles and
in the process, the cell eventually dies, releasing thousands of viral particles
into the organism.
• Viruses are specific for their hosts, and different strains exist that infect
bacteria, plants and animals.
Immunity
• What is immunity?
• The immune system is your body’s way of helping to protect you from
infection. When your body is infected by viruses, bacteria or other infectious
organisms (e.g. a fungus or parasite), it undergoes a process of fighting the
infection and then healing itself.
• As a result of this, the next time your body encounters the same organism,
you will be 'immune' to this infection. This means that you are less likely to
get the same disease again, or if you do, the infection will be less severe. This
is the principle behind vaccination.
The War Against Viruses
• The body’s defense system usually responds to viral infections by producing
specific antibodies, which act against a virus in the immune response. This
often leads to protection against repeated infections with the same virus
(immunity).
• Sometimes the virus is not completely eradicated from the body and
remains dormant in the cells. This can cause a flare-up on another occasion,
such as some herpes infections which cause cold sores. Another example is
the chicken pox virus, which can cause the shingles disease years after the
original infection.
Viral Infections
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Despite the body’s defenses, viral infections claim the lives of millions of people each
year and are responsible for an even greater number of illnesses.
Diseases such as measles, meningitis and polio are caused by viruses, as are more
recent diseases such as AIDS, ebola and the avian flu.
Treating viral infections is particularly difficult because viruses live within host cells and
so cannot be easily targeted.
Antibiotics, such as penicillin are effective against bacteria because they can target a
structure such as a cell wall, but there no equivalent structures to target in viruses.
Another problem is the speed at which the viruses multiply. They have often spread
through the organism by the time the symptoms appear.
In addition, virus particles have a tendency to mutate rapidly, which changes their
susceptibility to drugs.
Vaccines
• Vaccines- first introduced in the 18th century, have been successful in
preventing viral infections (prophylactic treatment). Vaccines work by
stimulating the body to produce specific antibodies.
• Successful vaccination programs have reduced the incidence of diseases such
as cholera, polio, and measles. Other viruses such as smallpox have been
completely eradicated.
• However, the effectiveness of some vaccines is limited by mutations in a virus.
For example, flu vaccines are only useful against known strains, but as these
change through mutation, different vaccines usually have to be prepared and
administered every year.
Antiviral Medications
• The main strategy to treat viral infections is the administration of specific
medicines known as antivirals.
• These medicines interfere in some way with the viral life cycle and so prevent
the release of new viral particles from the cell.
• Some antivirals work by altering the cell’s DNA so the virus cannot use it to
multiply and others work blocking enzyme activity within the host cell, which
prevents the virus from reproducing.
Influenza Virus
Hemagglutinin and Neuraminidase
• Hemagglutinin (H) is a glycoprotein that enables the viral particle to
recognize and bind with the host cell before it enters it.
• Neuraminidase (N) is an enzyme that catalyzes a cleavage reaction
which allows the new viral particles to escape from the host cell and
spread infection. The enzyme snips off a type of sugar molecule, sialic
acid, from glycoproteins on the surface of the host cell membrane.
Hs and Ns
Inhibitors
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The enzyme neuraminidase binds to the substrate (the substance on
which an enzyme acts), the sialic acid, at a specific region known as the
active site.
By determining the structure of neuraminidase, researchers were able
to design a molecule which could bind at the active site and so block the
binding of substrate. Chemicals that interfere with this binding are
called inhibitors and usually have a specific fit with the enzyme.
Neuraminidase Inhibitors
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The first neuraminidase inhibitors were designed by a team in Australia, and led to
the production of zanamivir (Relenza) which was approved for use in 2000. It was
closely followed by the production of oseltamivir (Tamiflu).
Both drugs have a chemical structure similar to sialic acid and so are able to bind at
the active site in neuraminidase.
This class of drugs is active against both influenza A and B viruses.
Tamiflu and Redenza are claimed to reduce the symptoms of the flu and shorten
the time of its effects, but must be taken within 48 hours of the appearance of
symptoms.
HIV infection
HIV is a Retrovirus
• One of the problems of HIV infection is that the very cells meant to
initatiate an immune defense, the CD4 T cells, are the same ones targeted
for infection by HIV.
• In the process, the CD4 cells are killed, and the body is unable to trigger an
immune response, which leaves the body open to opportunistic infections.
• There are three main reasons why HIV is so difficult to defeat:
1. The virus destroys helper T cells, the very cells in the immune system that
defend the body against the virus.
2. The virus tends to mutate very rapidly, even within a patient.
3. The virus often lies dormant within host cells, so the immune system has
nothing to respond to.
Antiretroviral Drugs
Antiretroviral Drugs
Antiretroviral Drugs
• Inhibitors of the reverse transcriptase enzyme include AZT, also known as
zidovudine, which was the first antiviral drug to be approved.
• It has been found that the best results occur when a combination of different
antiretroviral drugs are used.
• Combination treatments usually include two different reverse transcriptase
inhibitors, plus a third drug.
• The cost for most combination treatments is approximately $12,000 per
patient per year
Antiretroviral Drugs
• As more drugs become available, doctors can now consider how to prescribe
drugs to individual patients.
• Antiretroviral treatments need to be sustained throughout life.
• Research on developing a vaccine for HIV/AIDS is ongoing. However, the
development of a vaccine to prevent HIV has not been possible.