Lecture 9: Antiviral agents and targets Flashcards
What is the objective of antiviral therapy
to inhibit viral replication while eliciting minimal toxicity to the host
t or f: antivirals have to be administered early to be efficacious for acute infections
true
what is the most common antiviral used and for treatment of what
nucleoside analogs for tx for herpesviruses and retroviruses
what are the 4 classifications of antiviral drugs
- Immune modulators
2, anti-influenza antivirals - DNA/RNA synthesis inhibitors
- Protease, integrase, and entry inhibitors
what do DNA/RNA synthesis inhibitors target (what viruses)
herpesviruses and retroviruses
what do proteases, integrases, and entry inhibitors target (what viruses)
retroviruses
immunomodulators are substances that either ___ or __ the immune system
stimulate or suppress
What type of antiviral is type I interferon
immunomodulator
how does type I interferon work
acts by triggering RNAses to degrade viral RNA and protein kinases that inhibit host and viral protein synthesis
what drug has been shown to be effective against FIV and FeLV
Feline interferon-omgea- type I interferon
what are the 3 broad classes of anti-influenza anti-viral agents
- Adamantane derivatives
- Neuraminidase inhibitors
- Polymerase inhibitors
what anti-vital has been used against influenza A viruses
adamantanes
how do adamantanes work (amantadine, rimantadine). Understand how normal process works and how adamantanes block
block the uncoating step of life cycle,
Normal uncoating: endosomal acidic action, active viral M2 channel protein allows H+ ions to enter virion, viral M1 matrix protein dissociates results in viral uncoating- adamantanes block the uncoating
hemagglutinin binds to __which is used to __
sialic acid, adhere to host cells
viral Neuraminidase cleaves __, releasing __
sialic acid, releasing viruses from membranes
what type of drug is oseltamivir
Neuraminidase inhibitors
what are Neuraminidases used against
influenza A and B viruses
how do neuramindases inhibitors work/sialic acid analogs
binding neuramindase and preventing enzymatic activity- inhibits viral release from membrane and prevents viruses from infecting new host cell
what is the mechanism of resistance to oseltamivir
mutations in neuroamindase that arise randomly during RdRp mediated replication, followed by selecting
what drug has been shown to improve clinical signs against parvovirus
oseltamivir
how does oseltamivir work for parvovirus since it does not contain Neuraminidase
acts on bacterial Neuraminidase from enteric bacteria
how do purine analogs: acyclovir and derivatives and pyrimidine analogs: cidofovir work
interfere with viral DNA synthesis
how do purine analogs: remdesivir work
Interfere with viral RNA synthesis
how do pyrimidine analogs: zidovudine work
interfere with retroviral DNA synthesis
how do non-nucleoside reverse transcriptase inhibitors work
interfere with retroviral DNA synthesis
how do nucleoside analogs work
inhibit viral DNA polymerase and have chain termination activity
nucleoside analogs are converted to __ in host cell
triphosphate nucleotides (active form_
what are nucleoside analogs primarily effective against
herpesviruses
acyclovir is an analog of __ and what is it used to tx
analog of deoxyguanosine that selectively inhibits replication of herpesvirus, primarily alpha-herpesviruses
how does acyclovir become its active form
converted to ACV-P by the viral enzyme thymidine kinase
acyclovir is a competitive inhibitor of __
viral DNA polymerase
ACV-triphosphate has much higher affinity for __
viral DNA polymerase
incorporation of ACV-triphosphate results in __
chain termination
How does acyclovir achieve selective toxicity
uninfected cells do not convert ACV to ACV-P
how does resistance occur with acyclovir
mutations to viral thymidine kinase or DNA polymerase
what are the derivatives of acyclovir (prodrugs)
- Valacyclovir- converted to ACV
- Famciclovir- converted to penciclovir
what are valacyclovir and famciclovir used against
alphaherpesvirus
all acyclovir derivatives require __ by virally encoded enzymes. How does that occur
phosphorylation, via viral thymidine kinase
vidarabine is an analog of __
adenosine
what is the mechanism of action for vidarabine
interferes with viral DNA polymerase activity
what is vidarabine used for
FHV-1 ocular infections in cats
Remdesivir is a __ analog
adenosine
how does remdesivir work
inhibits viral RNA-dependent RNA polymerase
what is remdesivir used to tx
FIP caused by feline coronavirus
cidofovir is an analog of __
nucleoside deoxycytosine
how does cidofovir work
inhibition or polymerase activity and chain termination
What is the mechanism of resistance against cidofovir
mutations in DNA polymerase
what does cidofovir tx
- Herpesviruses- eye infections in cats
- Adenovirus
- Pox viruses
- Papilloma viruses
what does zidovudine tx
cats with severe dental inflammation or neurological disease
Zidovudine is an analog of __, containing __ of sugar
thymidine, azide
zidovudine is a __ inhibitor
nucleoside reverse transcriptase inhibitor
how does zidovudine work
inhibition of viral reverse transcriptase activity, synthesizes DNA from DNA
what is zidovudine used to tx
FeLV in cats
How do entry inhibitors work
prevent viral attachment/entry into the host cells
how do integrase inhibitors (raltegravir) work
prevent incorporation of the pro viral DNA into the genome of host cell
how do protease inhibitors work
prevent cleavage of pro-protein into functional polypeptides
