3 - antivirals Flashcards
what are viruses
obligate intracellular parasites
what does it mean to be an obligate intracellular parasite
they rely on host biosynthetic machinery to reproduce
they dont make their own proteins
what is a virion
when viruses are not inside a cell, they are independent particles
what do virions consist of
double or single stranded DNA protein coat lipid envelope(derived from host cell)
what is a capsid
protein coat to keep genetic material inside
what are the antigenic glycoproteins
important to determine which cells the viruses will affect
in the lipid envelope
what is viral range
the group of cell types that a virus can infect
what is a bacteriophage
virus that only infects bacteria
what are animal and plant viruses
viruses that infect animals and plants
why are animal viruses able to cross phyla
they cant, they often only infect closely related species (humans and primates)
what are the three shapes of viruses
helical
icosahedral
complex (bacteriophages)
what is pathogenicity
ability of virus to cause disease and replicate within host
what is virulence
degree of virulence (how sick host gets)
what is latency
the concept that some viruses can remain dormant in organisms for a long time
(ex: chicken pox)
what are carriers
people that chronically infected and serve as reservoirs of infectious virus
where does the chicken pox virus stay in the body
dorsal root ganglia
what are the 4 steps of lytic cycle of viral replication
absorption(into host cell), penetration(of genetic material into cytoplasm or host cell), replication(make DBA or RNA), release (virions released into environment)
what determines the host range of a virus and begins the infection process
the surface of viruses (proteins that bind to receptors proteins on host cell)
what are the classifications of viruses (not structure)
RNA, DNA, single stranded, double stranded
do DNA viruses come with their own DNA
yes
what happens once DNA viruses enter the host cell
their DNA is transcribed into mRNA by host cell polymerase, then translated into proteins
what makes poxviruses so special
they carry their own RNA polymerase and replicate in the host cell cytoplasm
but they use host cell to translate
how can RNA viruses replicate
either the mRNA can be transcribed from RNA to mRNA (using enzymes in virion)
or the viral RNA itself can act as mRNA
how do RNA viruses get RNA polymerase
they make it themselves (they use host machinery to make it from their own RNA)
where do most RNA viruses complete their replication
in the host cell cytoplasm
where do influenza viruses complete their replication
transcribed in the host cell nucleus
what are special about retroviruses
have RNA genome that directs the formation of a DNA molecule
how does RNA go to DNA with retroviruses
using reverse transcriptase (RNA dependent DNA polymerase)
what happens to the dsDNA made from retroviruses
it is integrated into the chromosomal DNA of host cell
how is retroviral DNA transcribed
by host machinery into RNA
how do most retroviruses kill their host cells
they dont kill their host cells initially, they infect them and create a lot of infected daughter
what can vaccines consist of
live attenuated or killed viruses
or viral proteins
where can anti-viral drugs exert actions
viral entry
nucleic acid synthesis
protein synthesis and processing
viral packaging and release
what does virustatic mean
it does not kill the virus, they just impede infection/ stop replication
are antivirals virustatic or cidal
static
what is acyclovir
nucleoside analog which viruses use for replication
why does acyclovir result in DNA chain termination
it lacks OH group which is important for forming the backbone of the DNA molecule
what infection is acyclovir used for
herpes
what is thymidine kinase
made by herpes virus that phosphorylates acyclovir
what must happen before acyclovir can be incorperated into DNA
it must be phosphorylated
how is acyclovir phosphorylated
by thymidine kinase
why does acyclovir mess up human DNA
because thymidine kinase has a affinity for acyclovir 200x than that of mammalian enzyme
what is the major excretion route of acyclovir
renal excretion
how can acyclovir be administrated
topical, oral, intravaneous, butt
what is the oral bioavailability of acyclovir
how does it change with dose
10-30% and decreases with increasing dose
what is the half life of acyclovir
2.5h
how does acyclovir resistance happen
impaired production of thymidine kinase or altered specificity
what does amantadine do (broad)
inhibits viral uncoating (early step in replication)
what virus does amantadine affect
influenza A
what does amantidine do (specific)
blocks H+ transfer through M2, blocking acidification and initiation of transcription
what is the M2 protein
a proton ion channel which allows acidification of the virus core (activates viral RNA transcriptase)
what does RNA transcriptase require to be activated
acidification of the virus core
what happens to the viral core at the onset of infection
it becomes acidic
does amantidine protect against influenza A
yes
but there are resistant strains
does amantidine protect against influenza B
no
what is the alternative if someone is not able to get vaccine (immunocompromised)
seasonal prophylaxis using anti-virals
what is zanamivir
anti influenza drug
how does zanamivir work
inhibits neuroaminidases produced by influenza A and B (works after replication) to impede viral spread
what do neuroaminidases do
cleave sialic acid residues from viral proteins which enables virus to be released from the host cell
what kind of virus is HIV
lentivirus (retrovirus)
what are special about lentiviruses
they lead to chronic persistent infection with gradual onset of clinical symptoms
what kind of cells does HIV attack
CD4+ T cells
what happens to the CD4+ T cells when infected to HIV
the levels decline below a critical level, leading to AIDS (lose cell mediated immunity)
how does replication change after HIV infection
it doesnt, replication is constant
what is HAART
highly active antiretroviral therapy
target multiple pathways alone the infection route
what does maraviroc do
CCR5 receptor antagonist
blocks HIV from binding to the CD4 receptor on T cell
how does HIV infection begin (what attaches)
attachment of HIV envelope proteins (gp120) to CD4 and CCR5 receptors on the surface of T cells
what do HIV entry inhibitors intefere with
binding fusion and entry into cell
how does HIV reverse transcriptase enzymes work
synthesize DNA from HIV RNA using nucleosides in the host T-cells (RNA dependent DNA pol)
how do nucleoside reverse transcriptase inhibitors work
they are incorperated into the HIV DNA but lack 3’OH so it causes chain termination
why dont nucleoside reverse transcriptase inhibitors work on human cells
mammalian RNA and DNA polymerases are sufficiently distinct to permit a selective inhibition of viral reverse transcriptase rather than host cells
what are non nucleoside reverse transriptase inhibitors
drugs that block the transcription of viral DNA but they dont compete with nucleoside triphosphates
how do non nucleoside reverse transriptase inhibitors work
they bind to a different site than NRTIs (they bind to reverse transcriptase) and inhibit the activity of reverse transcriptase
what are integrase strand transfer inhibitors
blocks the integration of viral DNA into the host gene
what is integrase
viral enzyme that inserts viral genome into the DNA of the host cell
what is raltegravir
integrase strand transfer inhibitors
what are protease inhibitors
at latest stage of viral transcription process, blocks final maturation and release of HIV virion into the enviro
blocks aspartate proteases so that virion particles never reach their mature form
what is aspartate protease
a viral enzyme that cleaves precursor proteins to form the final structure proteins of the mature virion core
