Microbiology 6: Prevention and treatment of viral disease Flashcards
Differentiate between prophylactic and therapeutic approaches to virus control
Most vaccines are used prophylactically. Prophylaxis- is preventing disease before the aetiologic aggent is acquired, by vaccination or giving drug before infection Most antiviral drugs are given after the person is infected as a therapuetic agent.
Describe the process for the attenuation of virus to make a live virus vaccine
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Describe the process for recombinant attenuated virus vaccines
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Describe the process for subunit vaccines
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Describe how you would make an inactivated virus
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Explain why it is difficult to develop drugs which selectively act against viral infections?
Viruse are intracellular obligate parasites. This makes them difficult to combat with chemotherapeutic agents. It is hard to find a stage of the virus replication cycle to attack with a drug that does not involve a host function. e.g. A drug that inhibited viral translation for example would knock out our own cells’ ability to translate mRNA’s
Summarise the general strategy of designing drugs which target infectious agents but not the patients own cells
The drugs target viral enzymes that have been found to differ from any enzymes used by our own cells.
What do most antiviral drugs target?
In reality most antiviral drugs target viral enzymes, often acting as substrate analogues.
Identify stages in the life cycle of a viruses which could potentially allow therapuetic intervention
In principle, all the steps in the virus life cycle ranging from entry to release can be explored as molecular targets for antiviral therapy.
List examples of classes of drugs which have been used sucessfully in antiviral therapy
Nucleoside Analogues Protease inhibitors ion channel blockers
Explain the specific strategy of using acyclovir and other nucleoside analogues as antiviral drugs
Acyclovir is a nucleoside analogue It is given to the patient in an unphosphorylated form(inactive), a prodrug, that means it cannot be used as a substrate in DNA replication. Its specificity comes from the fact that it is only converted into its active form inside a cell that is already infected by herpes virus. This is because the virus encodes an enzyme called thymdine kinase that can phosphorylate the drug. Once acyclovir triphosphate is incoporated into the growing DNA chain in the herpes virus genome, it terminates the reaction because it lacks the OH groups by which the next nucleoside would normally attach. add pic
What is Zidovudine AZT used to treat?
HIV
What is HAART used to treat?
HIV
How do neuraminidase inhibitors work?
Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidase inhibitors (NAIs) are a class of drugs which block the neuraminidase enzyme. They are commonly used as antiviral drugs because they block the function of viral neuraminidases of the influenza virus, by preventing its reproduction by budding from the host cell.
How does Tamiflu and Relenza work?
The viral enzyme neuraminidase destroys cell surface receptors. Tamiflu is a neuraminidase inhibitor in that it resembles the cell surface receptors
Neuraminidase inhibitors (NAIs) are a class of drugs which block the neuraminidase enzyme. They are commonly used as antiviral drugs because they block the function of viral neuraminidases of the influenza virus, by preventing its reproduction by budding from the host cell.
Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replication.
If you look at the diagram below this cleavage allows the virus to break free and escape the host cell.
What is the mechanism of action for Zidovudine and AZT?
Nucleoside Analogue.
It was the first anti HIV drug but resistance quickly emerged.
It is a nucleoside analogue reverse transcriptase inhibitor used to treat HIV. Zidovudine is phosphorylated by viral thymidine kinase, forming zidovudine triphosphate. Reverse transcriptase has a high affinity for this and incorporates it into the viral DNA it is producing. It acts as a chain terminator because it has no OH on the 3’ C, hence no phosphodiester bond can form.
What is HARRT and why is it used?
It stands for Highly Active Anti-Retroviral Treatment. It is a combination of 3 or 4 antiretroviral drugs used to treat HIV. It is used because even if the virus has developed resistance to one over time, one of the other drugs will still be able to affect viral replication or protein synthesis. It enables the immune system to fight the virus.
Name an example of an intergrase inhibtor and describe its mechanism of action?
Raltegravir –
Blocks virus/host
DNA transfer
Name and example of an protease inhibitor and describe its mechanism of action?
Viral Protease. When viral RNA is translated into a polypeptide sequence, that sequence is assembled in a long chain that includes several individual proteins (reverse transcriptase, protease, integrase). Before these enzymes become functional, they must be cut from the longer polypeptide chain.
Atazanavir (generally taken with Ritonavir)
Name and example of an Entry inhibitor and describe its mechanism of action?
CCR5,CXCR4 inhibitors
e.g. Maraviroc
Blocks gp120/CXCR4
interaction
Enfuvirtide
Binds HIV gp41 preventing
Membrane fusion
pore formation and entry
