antivirals Flashcards
- Define what is meant by a virus
Infectious, obligate, intracellular parasites
It is absolutely dependent on the cell machinery of the host cell to replicate Can have DNA or RNA genome
- What size do viruses range from in diameter?
10nm up to a micron
- What is the cell membrane of a non-enveloped virus made from?
pure protein
- What is meant by a tegument?
- What is the central dogma?
A bunch of proteins in coat encapsulated within an envelope
Process by which genetic instructions are converted into a functional product DNA converted into RNA by transcriptase RNA used to make protein by ribosomes of the cell
- What does it mean if a virus carries their RNA in the negative sense?
Complementary strand of mRNA
Before they translate genome into proteins They copy negative sense back into complimentary copy which is positive sense to translate this into ribosomes
- How do RNA viruses compensate for RNA genomes being shorter than DNA genomes
- What does Reverse Transcriptase do?
Use complex coding strategies to make more proteins than expected from small RNA genome
Makes DNA from host's nucleotides using the Virus' RNA as a template
- Do RNA viruses & Retroviruses use their own machinery to replicate and how does this affect their mutation rate?
They use their own polymerase to replicate
These lack proof reading, so higher mutation rate
- In cultured cells, why are some genes in virus’ genome lost?
These genes might modify the host’s immune response to give the virus a survival advantage
However, there is no immune system in cultured cells
- What are segmented genomes and how do they affect the virus?
Allow an additional easy form of recombination known as, reassortment
If different strains of virus enter same host cell, the DNA can be mixed up to give a mutated virus But also impose more difficult packaging strategies
- Describe the stages of Virus Replication
Attachment - of virus’ attachment proteins to the cell membrane receptors
Insertion - of nuclear capsid with viral genome into the cell Translation - viral genome into proteins by host cell ribosomes and machinery Assembly - of viral proteins to form viral material Exocytosis - virus leaves the host cell, if enveloped, then the cell membrane of host cell is used to make the lipid envelope of the virus
- What is meant by the cytopathic effect?
- What do viral material form on cell monolayers?
Death of the cells, caused by the virus
Could be due to shut down of host protein synthesis or accumulation of viral proteins to form plaques
plaques
- What is meant by virus morphology?
- Where are the lipid envelopes of viruses derived from?
The shape or look of a virus
From lipid membrane of the cell
- How can you find out how many virus particles are in a particular preparation of virus?
Making dilutions o viral stock and putting them onto monolayers of cells
After 2/3 days, count number of plaques formed (clear holes) Plaque Assay Method
- What is Syncytia?
Viruses with surface proteins that can fuse at neutral pH often fuse cells together
Syncytia assay is also a method of finding out how may virus particles there are in a certain sample
- What is Syncytia?
Viruses with surface proteins that can fuse at neutral pH often fuse cells together
Syncytia assay is also a method of finding out how may virus particles there are in a certain sample
- How can you use PCR with an RNA genome?
Convert RNA to DNA
Then PCR allows the specific primers to amplify the viral DNA
- How can serology be used to detect a virus in a patient?
Take blood from patient and look at the serum
To see whether there are any antibodies that are specific to that particular virus
- Why is RT-PCR used to detect SARS CoV2?
- What is meant by the therapeutic index?
Because SARS CoV2 only contains RNA
Ratio between how much drug you have to use in order to control virus and how much a patient taking the drug feels the side effects
- Give some of the ways that antiviral drugs work?
Some will target the viral enzymes - increased understanding of structure of viral components and enzymes can lead to rational drug design
Some act as nucleoside analogues to inhibit or interfere with nucleic acid replication but need to achieve some sense of specificity for viral polymerase
- What do Directly Acting Antivirals target?
Specific viral factors (specific to virus)
- What does a nucleoside analogue do?
Nucleoside analogues are synthetic, chemically modified nucleosides
They have very similar structures to nucleosides and block cellular division/viral replication by impairment of DNA/RNA synthesis or by inhibition of cellular or viral enzymes involved in nucleoside/tide metabolism
- Give 4 of the nucleoside analogues used to treat viruses
Acyclovir - Herpes
Zidovudine - HIV Remdesivir - Ebola Favipiravir - Influenza
- What is the best anti-viral agent with viral specificity?
- How does this agent work?
Acyclovir
Modified nucleoside incorporated into DNA Lack of 3 prime -OH prevents phosphodiester bond formation
- What makes this agent specific?
It is given to patients in un-phosphorylated form and needs to be phosphorylated to work
The thymidine kinase that forms acyclovir monophosphate is only formed by herpes virus family Higher affinity for viral DNA polymerase than for host cell polymerase
- What is remdesivir a nucleoside analogue of?
- What class of drugs do both Amantidine and rimantadine both belong to?
Adenosine
Causes chain termination 3 nucleotides downstream of incorporation -twists growing molecule so it cant be extended
Adamantanes
- What is amantidine?
- How does amantidine work?
Cyclic amines with bulky cage-like structures
only active against influenza A
Sits in the middle of tetrameric ion channel - M2 ion channel
H+ ions cannot enter core of particle and the virus is locked in endosomes
Initiation of infection is blocked as the ribonucleoproteins of influenza can no longer leave the virus to go to the nucleus
- What is one of the disadvantages of using amantadine?
Only takes single point mutation in genes coding for M2 ion channel for amantadine to no longer bind
Little cost to fitness and virus still maintains virulence and is transmissable
- Why is neuraminidase essential in the actions of influenza?
Cleaves bond between haemagluttinins on influenza and the sialic acid of the host cell membrane
This allows the virus to continue infecting more of the host's cells
what are the three neuraminidase inhibitors
- Why was Relenza not such a successful drug as Tamiflu?
sialic acid, relenza, tamiflu
Because the chemistry of Relenza means the virus more readily acquires resistance
What is Baloxavir
- What is meant by Biologicals?
anti influenza anti viral drugs targeting PA endonuclease- sub unit of RNA polymerase
Largely antibodies, derived from recovered individuals or produced in the laboratory from immortalised B-cells (Passive immunotherapy)
- Give 5 of the ways in which HIV replication can be inhibited?
Inhibiting entry of virus by stopping it from attaching to its receptors and co-receptors
Inhibit fusion of viral and host cell membrane
Targeting reverse transcriptase Target integrase (prevent DNA integrating with host DNA) Target proteases unique to viruses
- What is an immunomodulator?
- What is Dexamethasone?
- What is Toculizimab?
a chemical agent that modifies the immune response or the functioning of the immune system
Corticosteroid used for immunosuppressants Targets pro-inflammatory cytokine IL-6
What is palivizumab
humanized monoclonal antibody against the pre fusion F protein of RSV
what are the mechanisms of directly targeting antivirals against hepatitis C
protease inhibitors
NS5B polymerase inhibitor (an RNA polymerase)
non nucleoside polymerase inhibitors
NS5A target
What properties do antivirals against influenza must have
target unique or essential gene of function of the virus
be effective against the range of influenza types and strains
be easy to administer
few side effects for compliancy
how has HIV been cured before
Transplant bone marrow from those naturally resistant to HIUV because they have a mutation in their CRR5 receptor gene, so CRR5 is not expressed
So HIV cannot enter cells
