Anti-Virals Flashcards
What are viruses?
Obligate intracellular parasites
Which anti-viral has the highest level of specificity?
Acyclovir
What condition is acyclovir used to treat?
Herpes
Why is acyclovir so specific?
Given to patients in the unphosphorylated form, has to be phosphorylated from ACV to ACVMP, this is only done by thymidine kinase which is an enzyme only found in virally infected cells
How does acyclovir work as antiviral?
Works as a nucleoside analogue - acts as a chain terminator as it lacks an OH group in the 3’ direction meaning phosphodiester binds cannot form, preventing viral replication
What is a nucleoside inhibitor?
Molecule which looks like a nucleoside and is therefore incorporated into the genome, but actually inhibits viral replication
What is RNA in the negative sense?
A strand of RNA which is complementary to the mRNA
What sense of genetic material can ribosomes translate?
Positive sense
What is a virion
A virus particle outside the cell
Why can ribosomes not be targeted in anti-viral medications?
viruses uses human ribosomes to replicate, meaning they would be attacked
What is the central dogma?
DNA -> RNA -> proteins
Whose polymerase do viruses use to replicate?
Their own
Why do viruses have a high mutation rate?
They use their own polymerase to replicate which LACK PROOF READING
RNA is shorter than DNA. How do RNA viruses compensate for this?
They use COMPLEX CODING STRATEGIES to they can make more proteins than expected
Why is it useful for DNA viruses to be large?
They have room to acquire accessory genes which could make that virus better at modifying host immune response
What is a segmented genome and how does this impact viruses?
Allows easy recombination, therefore if different strains of the virus enter the host, reassortment can occurs, producing new variants
What is the size range of viruses?
1nm to 1 micrometer
What are two examples of neuramidase inhibitors?
Tamiflu and Relenza
What is Remdisivir a nucleoside inhibitor of?
Adenosine
How does Remdisivir work as a nucleoside inhibitor?
Acts as adenosine, and causes chain termination three nucleosides later, due to the chain twisting
What is Remdisivir used to treat?
Hepatits C
What is amantidine?
A adamantine
How does amantidine work as an antiviral?
Blocks the M2 ion channel which would normally allow H+ ions to enter into the endosome, meaning that the virus is trapped inside the endosome and therefore cannot replicate
Why is the use of amantidine not recomendable?
Most H3N2 viruses are resistant to it
How do NA inhibitors work?
They block the action of neuramidase preventing the virus from being released from the cel
Normally, NA works by cleaving the sialic acid / HA binding which the virus does to latch into the host cell, allowing the virus to leave
What are tamiflu and relenza used to treat?
Influenza
What is the lipid envelopes of viruses derived from?
The host cell membrane
What is the cell membrane of a non-enveloped virus made from?
Pure proteins
In cultured cells, why are some genes in virus’ genome lost?
Some genes are used to limit the immune response of the host cell against the virus to give the virus an advantage, however there is no immune response in cultured cells therefore these genes are not needed
What are the stages of viral replication?
Attachment Insertion Translation Assembly Exocytosis
What do direct acting antivirals target?
Specific viral factors
What are biologicals?
Antibodies which are derived from recovered individuals or synthesized in the lab from immobilized B cells - given directly into the blood
What anti-virals are used to treat Hepatitis C?
Direct Acting Antivirals
Between Relenza and Tamiflu, which is more effective and why?
Tamiflu - the chemistry of relenza means the virus can more readily acquire resistance so less effective
Acyclovir and ribavirin are both antiviral agents that act as nucleoside analogues. Why is acyclovir effective against herpes simplex virus but not influenza?
c) Because acyclovir is only converted to its active form inside a cell infected by herpes virus that encodes thymidine kinase, and influenza virus does not encode such an enzyme.
Tamiflu (oseltamivir) is an antiviral drug that can be used to treat influenza virus infection. The mechanism of action is:
a) To inhibit the neuraminidase enzyme that removes sialic acid from the infected cells surface and allow onwards spread of new virus particles.
Why might a patient with chronic hepatitis C virus treated with an HCV protease inhibitor drug show a loss of a positive viral response over time?
The virus has acquired resistance to the drug.
The patient has continued in high risk lifestyle and acquired a second infection with a different strain of HCV.
The patient has stopped taking the drug because it gave unpleasant side effects.
Two people in the world are believed to have been ‘cured’ of HIV. How has this been achieved?
They have undergone bone marrow transplantation with cells from a CCR5 delta 32 donor.
what is PrEP for HIV?
Pre exposure Prophylaxis (PrEP) means taking HIV antivirals daily to prevent possible HIV infection during sex with an infected partner.
BHIVA guidelines require that people have an HIV test before going on PrEP. Why is this so important?
If the person is already HIV infected you don’t want to be giving them treatment with only two drugs as resistance can likely be selected more easily than the standard which is three drugs at once.
Single use of antiviral agents increase the risk of resistance. How is this overcome?
Through the use of combination therapy - this means the chances of anti-viral resistance is much less likely, as the virus would have to have a gene mutation against every single drug in the combination
What are four stages of HIV replication which are targeted in combination therapy?
- Viral entry inhibition
- Integration of viral genome inhibition
- Protease inhibition
- Reverse transcriptase inhibitors
