Antiviral Therapies Flashcards
(45 cards)
Microcephaly
Zika virus
Definition of a virus
Obligate intracellular parasites
What is the composition of a virus
Genome comprised of DNA nad RNA
Viral genome is replicated and directs th synthesis
Examples of symmertrical protein capsid
Adenovirus
Picornavirus
Calicivirus
Non-enveloped
Examples of eneveloped virus
Lipid envelope derived from host membrane
Pleimorphic: measles virus (variation in size)
Ebola virus
Examples of combination of capsid and envelope
Herpes virus
How is a virus named
The disease: polio
Person who discovered it: epstein barr
Place it was discovered: coxsackievirus
Part of the body affected: rhinovirus, hepatitis
Way it is spread: dengue, influenza
What is the negative sense
Complimentary strand of the messenger RNA
What are the consequences of viral genome type
RNA viruses and retroviruses use own polymerase to replicated - lack proof reading capacity high mutation rate
RNA less stable - size is limited
RNA viruses use complex codign stragies to make more proteins
DNA are big - accessory genes are not essential but can modify the host immune response, often lost in passage in culture
Segmented genomes - allows additional easy form of recombination, but imposes more difficult packaging stategies
How many influenza virus are made for every 1 entering the cell
1000 are made
What is the cytopathic effect
Death of the cell caused by virus
Lysing of the cell
Shut down of host protein synthesis or accumulation of viral proteins
Viruses form plaques
As the virus has replicated, it kills cells and leaves a hole which is stained clear
How is plaque assay useful
Can see how many viruses present
What si syncytia assay
Viruses with surface portein that fuse cells together
HIV
Viral diagnosis
Genome: PCR, RT-PCR
Antigen: IFA, ELISA - use antibodies to stain cells
Virus particles: electron microscopy
Cytopathic effect - virus isolaiton
Antibodies against virus - serology
How do we manipulate viruses
So small they can be synthesised
Introduce synthetic DNA or RNA - driven to replicate
Allows reverse genetics - engineer vaccinations
Why is it hard to treat viruses
Infect host cells - cannot target those
Have to find things that viruses do that host cell doesn’t
What do most of the antiviral drugs do
Target viral enzymes - by rational drug design
Nucleoside analogues - inhibit with nucleic acid replication - however need to element of specificity
What is acyclovir
Nucleoside analogue
Looks like guanosine
Whole bottom half is missing so 3’ - OH cannot attach in nuecleotide chain, prevention of phosphodiester bond
Chain terminator
Why is acyclovir so good for specificity
Exist in its unphophorylated form
Aciclovir can only be phosphorylated by viral thymidine kinase only encoded in herpes virus
Rest of the steps are using cellular enzymes
aciclovir tirphosphate has higher affinity for viral DNA polymerase than host cell
What is remdesivir
nucleoside analogue
analogue of adenose - chain termination 3 nucleotides downstream
it twists the shape of the molecule so no more nucleotides can be added
used for ebola but more recently used for COVID
What is important for an antiviral drug
Target a unique and essential gene
Be effective against a range of influenza types
Be easy to administer even to very sick patients
Few side effects
How does adamantanes/rimantadine work
Cyclic amines with bulky cagelike structures
Byproducts of petroleum refinement
Active against influenza A molecule
TARGET: Sit in the middle of a tetrameric ion channel specifically coded by influenza virus known as M2 ion channel
M2 allows H+ from acidic enviornment of endosome to virus core
Undo interactions holdign virus together
Release of genome by uncoating of virus
Resistance to adamantadine
Single point mutation on M2 for amantadine to no longer bind (S31N)
Little cost to fitness
Most H3N2 are resistant
H5N1 bird flu
Swine flue pH1N1
