Antiviral Drugs Flashcards
describe first, second, and third lines of defense
1st: mechanical, chemical, biological barriers
2nd: innate immune response
3rd: adaptive immune response
describe the 3 different kinds of vaccines
- inactivated: genome destroyed, capsid intact
- attenuated: extremely slow to replicate, “live” viruses
- genetically engineered: viral proteins produced by yeast cells, concentrated, and purified
6 barriers to finding effective antiviral drugs
- selective toxicity for virus fxns
- resistance due to rapid mutation
- intracellular - can’t use non-permeable drugs
- symptoms usually occur at height of viral replication
- latency or non-replicating phases hard to target
- limited capability for rational drug development
which viruses do we have antiviral drugs against?
- herpes simplex virus
- varicella-zoster virus
- CMV
- HIV
- influenza A and B
- hepatitis B and C
how do antivirals disrupt enveloped viruses?
- nonoxynol-9, or N9-detergent (emulsify lipid coat)
- HSV, HIV - citric acid
- Rhinovirus
how do antivirals disrupt viral attachment?
- neutralizing Ab’s that interfere w/ ability to infect
- interfere w/ receptor binding
- cause aggregation of virus particles
- receptor antagonists
- fusion inhibitors
what is an example of an antiviral receptor antagonist?
Maraviroc/Selzentry - CCR antagonist
binds to/changes shape of CCR5 receptor so it is not recognized by gp120 coreceptor binding sites
what is an example of an antiviral fusion inhibitor?
Enfuvirtide/Fuzeon - peptide mimic of HR2 region of gp41, inhibiting the action of the viral fusion protein gp41 of HIV
what are two examples of antivirals that disrupt viral uncoating?
Adamantanes (M2 inhibitors) - amantadine/symmetrel and Rimantadine/flumadine
- weak organic bases to treat Influenza A
- target M2 protein - disrupt H+ transport -> inhibits uncoating
- well absorbed orally, crosses BBB
- 90% excreted unchanged
- low toxicity, some hallucination with amantadine
how do antivirals interfere with nucleic acid synthesis?
-nucleoside analogs that inhibit viral polymerase by causing chain termination
nucleoside analogs that cause errors in replication and transcription
-non-nucleoside analogues
general mechanism of action for nucleoside analogues
- taken up by cells
- phosphorylated first by viral enzyme, then twice by cellular enzymes into triphosphate form
3a. inhibit DNA and RNA polymerase activity, w/ higher affinity for viral enzymes
3b. incorporated into growing DNA -> abnormal proteins or breakage
acyclovir: other names, what is it used to treat, describe it in terms of structure, in general what does it help with
valacyclovir (prodrug), penciclovir (cream), famciclovir (oral)
- drug used primarily for HSV-1, HSV-2
- purine mimic of 2’ deoxyguanosine
- decreased pain, speed healing of sores/blisters in chicken pox, herpes zoster, genital herpes
- prevent outbreaks of genital herpes
mechanism of action of acyclovir
- inactive acyclovir activated by phosphorylation of an OH by viral thymidine kinase
- host thymidine kinase adds two more phosphates -> active, triphosphate form of drug
- drug incorporated into growing DNA chain, but has no 3’ OH, so causes chain termination b/c another nucleotide cannot be added on
why will acyclovir not affect healthy cells?
acyclovir must be phosphorylated first by VIRAL enzymes… host enzymes cannot form the monophosphate form, therefore, they will not be affected
ganciclovir: other names, what is it used to treat, describe it in terms of structure, adverse effects, in general what does it help with
cytovene/ cymevene/ vitraset
- active against all herpes viruses including CMV
- synthetic analogue of 2’-deoxyguanosine
- still phosphorylated first by viral enzyme, then by cellular
- AE: bone marrow suppression (leukopenia, thrombocytopenia), CNS effects (headaches, behavioral, psychosis, coma, convulsions)
- drug of choice for CMV retinitis, pneumonis, colitis
