Three types of host defense against virus
Specific barriersNonspecific cellular barrierimmune system
Vaccine based on person exposure to ____ in order to make ______
chemically deactivated virusesAntibodies
Antiviral drugs generally inhibit ______ or _______
Nonspecific defenses (1st and 2nd lines)
1st = skin, mucous membrane2nd = WBC, antimicrobial proteins, inflammation
Third line of host defense is based on _____ and consists of _____ and ______
ImmunityLymphocytes and AB's
Three types of vaccines
Inactivated vaccine has destroyed _____, and intact ______
____ is an inactivated vaccine
Attenuated vaccine replicates ______. Examples are _____ and _____
Engineered vaccines have ____ that are produced by ________
viral proteinsyeast cells
Example of genetically engineered vaccine
Why do we need antivirals? (6 reasons)
--No vaccine or problems with them--Mutation--Reassortment--New infections--TIME to make vaccines--Immunosuppressive diseases
Antivirals -- barriers to making effective ones? (6)
Selective toxicityResistanceIntracellular bugsDelay of SymptomsLatent phase hard to targetLimited drug development
Successful drug intereferes with either...
Viral functionCell function that virus needs
There are antivirals against which viruses?
HSV, VZV, CMVHIVInfluenza A + BHep B + C
Six targets for antivirals (steps)
Before attachmentAttachmentPenetration/uncoatingReplication of genomeProtein synthesisAssembly/release
Viral disruption is effective against ______ viruses
Nonoxynol (N9) is a ______ against ___ and ____
Citric acid disrupts...
The first group of viral attachment blocking agents rely on _____. This interferes with ____ and causes ______
neutralizing antibodiesInterferes with Binding to receptorsCauses aggregation of viral particles
Maraviroc is a _______. What is its mechanism?
CCR antagonistChanges CCR5 shape so it cant bind gp120
Viral attachment blockers have three groups, which are...
Neutralizing antibodiesReceptor antagonistsFusion inhibitors
Fusion inhibitor example and general mechanism.
enfuvirtidestop HIV entry to CD4 cells
HR2 region of gp41(gp41 is fusion protein for HIV)
Uncoating blocker example (group and 2 examples)
Amantadine is a _______ that targets ______. This disrupts _______
Weak organic baseM2 proteinDisrupts H2 Transport, which inhibits uncoating of viral genome.
Amantadine is effective against....
Influenza ANOT B
Amantadine may cause ______ due to _______
Nucleic Acid Synthesis blocked by ___ and ____
Nucleoside anaolgsNon-Nucleoside analogues
Nucleoside analogs inhibit _____.
VIral polymeraseCauses chain termination
Nucleoside analogs that target viral Polymerase: examples (4 groups)
Nucleoside analogs can also cause ______. Examples? (3)
errors in replication and transcriptionRibavirinTFTIdoxuridine
Non nucleoside analog examples
Nucleoside analog mechanism
conveted by VIRAL (1) then CELLULAR (2) enzymes to TRIPHOSPHATE form
Triphohsphate form of Nucl. Analogs inhibit _____. Then they are...
DNA and RNA pol....Incorporated into DNA
The Nucl. Analogs have a ____ group that has been substituted for the usual ___ group
N3 (azide) group instead of OH
soluble, has better availability
Acyclovir Tx for
HSV 1 and 2
Acyclovir can be thought of as a ______
Acyclovir inhibits ______
Viral DNApol 100X AFFINITY
Acyclovir activated by
Acyclovir has ____ oral absorption rate
Gancyclovir is a synthetic analog of _______
Gancyclovir used for
CMV does not encode _____. So how does GCV work then?
Thymidine KinaseCMV encoded protein kinase P's gancyclovir
Gancyclovir- most common side effects
Bone marrow suppressionCNS effects
AZT is an analog of _____. What is the difference?
Thymidine 3' OH group replaced with Azide group (N3)
AZT inhibits _____
AZT isn't recommended as ___. Why?
monotherapy (due to resistance)
AZT Sides (3)
Cidofovir and Tenofovir work by _____
decreasing the amount of HIV in the blood
Cidofovir and Tenofovir structure
nucleoside analogscontain a PHOSPHATE attached to a SUGAR analog
Cidofovir and Tenofovir work independent of _____
Cidofovir and Tenofovir are substrates for ___ or ____
DNA polymerases or RT's
Cidofovir used for _____.SIdes?
CMV retinitis in AIDS ptsMay cause LIVER DAMAGE
Tenofovir used for
HBV and HIV
Telbivudine is an nucleoside analog of ___
Telbivudine is ____ by _____ enzymes
Phosphorylatedcellular Kinase enzymes
What form of Telbivudine is its functional form?This inhibits _______
Telbivudine-5-TriphosphateHBV DNA polymerase
Telbivudine used for
Viral polymerase properties (3)
Ribavirin is a _____ that causes ______
nucleoside analogerrors in replication and transcription
Ribavirin is an analog of _____, but contains ______
Guanosinean incomplete (open) ring
Ribavirin incorporated into _____The mechanism following this?
RNA pairs with URACIL or CYTOSINEinduces mutations in RNA viruses
Ribavirin active against...(Try to name all 8)
BROAD range of DNA virusesFlavi + ParamyxBunya + ArenaRetro + HerpesAdeno + Pox
Ribavirin mode of administration
aerosol or oral
Ribavirin major toxicity
Aerosol treatment of RSV in kids
TFT is a ____ analog. Mechanism?
ThymidineCF3 group added o the uracil -- BLOCKS base pairing
Phosphorylated by cellular enzymes
TFT drug form
TFT used for Tx of ____ caused by _____
topical Tx of EPITHELIAL KERATITIS caused by HERPESVIRUS
Idoxuridine substitutes for ___. Mechanism?
ThymidineThe iodine blocks base pairing
Idoxuridine used for...
HSV Keratoconjunctivitis and Keratitis
Idoxuridine phosphorylated by
Foscarnet is a ______ resembling ______
non nucleoside analogPyrophosphate
Foscarnet binds to
DNApol (at the pyrophosphate binding site)
Foscarnet used for ... (3)
HerpesvirusHIV Reverse TranscriptaseCMV retinitis in AIDS patients
Other NonNS Analogs
Nevirapine, Efavirenz, Delavirdine are considered _____
non-NS Reverse Transcriptase Inhibitors
Nevirapine, Efavirenz, Delavirdine mechanism of action
Bind RT directlyDisrupt DNApol catalytic siteBlock DNA pol activity *both RNA and DNA dependent*
Nevirapine, Efavirenz, Delavirdine doesn;t require...
Phosphorylation by cellular enzymes
Nevirapine, Efavirenz, Delavirdine -- used for
HIV-1(HIV2 has different structure RT)
Nevirapine, Efavirenz, Delavirdine --- used as part of ______
Raltegravir is a _______.Blocks ______.
Integrase Inhibitorblocks viral DNA integration
Interferon is a ______ that functions as a _____
Glycoprotein (cytokine)Protein synthesis inhibitor
Type 1 Interferons
Alpha and Beta
IFN alpha has ____ subtypes, and is made by what types of (viral infected) cells?
20 subtypesB cellMonocyteMQImmature DC's
IFN Beta has ____ subtypes, and is made by _____
IFN alpha aka _____
IFN Beta aka _____
Type 2 Interferonsaka..
IFN Gamma number of subtypes? Made by what cells?
3Activated T lymphocytes
Induction of Interferon (three things)
-dsRNA-interaction between sense / antisense mRNA-Interaction of some enveloped viruses
Three steps for Interferon mechanism
1. Infected cell releases interferon2. Binds a CSR on another cell3. Induces "antiviral state"
Effects of Interferon (2)
mRNA DEGRADED (protein synth inhibited)INHIBITS ribosome assembly
Interferon inhibits ribosome assembly via
EIF-2alpha *initiation factor
Interferon produced in response to infection does not affect __________
The INITIALLY infected cell
Interferon receptor induces what three things in affected cell?
2,5 oligoA synthaseRibonuclease LA protein Kinase
What is the function of 2,5 OligoA?
Activation of Ribonuclease L
Interferon has ___ activity
DNA viruses affected by interferon
RNA viruses affected by interferon
Other stuf (not DNA or RNA virus) affected by interferon
Breast + Lung cancerKaposi Sarcoma
Interferon is not ________ bioavailable. Routes?
orally*IM, SubQ, Topical
Antiviral agents affecting enzymatic functions of viral proteins (2 groups)
Protease InhibitorsNeuraminidase Inhibitors (Viral release inhibitors)
Protease Inhibitors (6)
"BRINTS"Boceprevrin, Ritonavir, Nelfinavir, Indinavir, Tipranavir, Saquinavir
Protease inhibitors especially effective against ____ and ___
Main mechanism behind protease inhibitors
stop cleavage of polyproteins so they cant be used for viral assembly
Protease inhibitors not recommended as ____
Neuraminidase inhibitors (2)
Zanamivir Oseltamavir (O shit my Tamiflu doesn't work)
NA inhibitors treat A, B, or both?
Neuraminidase functions by catalyzing....
cleavage of Sialic Acid (attached to glycoproteins)