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Virology > Lecture 3 - Antivirals > Flashcards

Lecture 3 - Antivirals Flashcards

1
Q

Three types of host defense against virus

A

Specific barriersNonspecific cellular barrierimmune system

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2
Q

Vaccine based on person exposure to ____ in order to make ______

A

chemically deactivated virusesAntibodies

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3
Q

Antiviral drugs generally inhibit ______ or _______

A

ReplicationAttachment

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4
Q

Nonspecific defenses (1st and 2nd lines)

A

1st = skin, mucous membrane2nd = WBC, antimicrobial proteins, inflammation

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5
Q

Third line of host defense is based on _____ and consists of _____ and ______

A

ImmunityLymphocytes and AB’s

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6
Q

Three types of vaccines

A

InactivatedAttenuatedEngineered

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7
Q

Inactivated vaccine has destroyed _____, and intact ______

A

genomecapsid

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8
Q

____ is an inactivated vaccine

A

Polio

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9
Q

Attenuated vaccine replicates ______. Examples are _____ and _____

A

SlowlyChickenpox, MMR

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10
Q

Engineered vaccines have ____ that are produced by ________

A

viral proteinsyeast cells

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11
Q

Example of genetically engineered vaccine

A

Hep B

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12
Q

Why do we need antivirals? (6 reasons)

A

–No vaccine or problems with them–Mutation–Reassortment–New infections–TIME to make vaccines–Immunosuppressive diseases

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13
Q

Antivirals – barriers to making effective ones? (6)

A

Selective toxicityResistanceIntracellular bugsDelay of SymptomsLatent phase hard to targetLimited drug development

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14
Q

Successful drug intereferes with either…

A

Viral functionCell function that virus needs

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15
Q

There are antivirals against which viruses?

A

HSV, VZV, CMVHIVInfluenza A + BHep B + C

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16
Q

Six targets for antivirals (steps)

A

Before attachmentAttachmentPenetration/uncoatingReplication of genomeProtein synthesisAssembly/release

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17
Q

Viral disruption is effective against ______ viruses

A

enveloped

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18
Q

Nonoxynol (N9) is a ______ against ___ and ____

A

DetergentHSV, HIV

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19
Q

Citric acid disrupts…

A

rhinovirus

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20
Q

The first group of viral attachment blocking agents rely on _____. This interferes with ____ and causes ______

A

neutralizing antibodiesInterferes with Binding to receptorsCauses aggregation of viral particles

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21
Q

Maraviroc is a _______. What is its mechanism?

A

CCR antagonistChanges CCR5 shape so it cant bind gp120

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22
Q

Viral attachment blockers have three groups, which are…

A

Neutralizing antibodiesReceptor antagonistsFusion inhibitors

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23
Q

Fusion inhibitor example and general mechanism.

A

enfuvirtidestop HIV entry to CD4 cells

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24
Q

Enfuvirtide mimics…

A

HR2 region of gp41(gp41 is fusion protein for HIV)

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25
Q

Uncoating blocker example (group and 2 examples)

A

Adamantanes–amantadine–rimantadine

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26
Q

Amantadine is a _______ that targets ______. This disrupts _______

A

Weak organic baseM2 proteinDisrupts H2 Transport, which inhibits uncoating of viral genome.

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27
Q

Amantadine is effective against….

A

Influenza ANOT B

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28
Q

Amantadine may cause ______ due to _______

A

HallucinationDopaminergic action

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29
Q

Nucleic Acid Synthesis blocked by ___ and ____

A

Nucleoside anaolgsNon-Nucleoside analogues

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30
Q

Nucleoside analogs inhibit _____.

A

VIral polymeraseCauses chain termination

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31
Q

Nucleoside analogs that target viral Polymerase: examples (4 groups)

A

Acyclovir, gancyclovirAZTCidofovir/TenofovirTelbivudine

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32
Q

Nucleoside analogs can also cause ______. Examples? (3)

A

errors in replication and transcriptionRibavirinTFTIdoxuridine

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33
Q

Non nucleoside analog examples

A

FoscarnetNevirapine

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34
Q

Nucleoside analog mechanism

A

conveted by VIRAL (1) then CELLULAR (2) enzymes to TRIPHOSPHATE form

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35
Q

Triphohsphate form of Nucl. Analogs inhibit _____. Then they are…

A

DNA and RNA pol….Incorporated into DNA

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36
Q

The Nucl. Analogs have a ____ group that has been substituted for the usual ___ group

A

N3 (azide) group instead of OH

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37
Q

Valacyclovir is…

A

soluble, has better availability

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38
Q

Penciclovir form:

A

cream

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39
Q

Famciclovir form:

A

Oral

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40
Q

Acyclovir Tx for

A

HSV 1 and 2

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41
Q

Acyclovir can be thought of as a ______

A

purine mimic

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42
Q

Acyclovir inhibits ______

A

Viral DNApol 100X AFFINITY

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43
Q

Acyclovir activated by

A

Thymidine kinasesViralHostHost

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44
Q

Acyclovir has ____ oral absorption rate

A

15-30%

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45
Q

Gancyclovir is a synthetic analog of _______

A

2’-deoxy-guanosine

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46
Q

Gancyclovir used for

A

CMV— retinitisPneumoniaColitis

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47
Q

CMV does not encode _____. So how does GCV work then?

A

Thymidine KinaseCMV encoded protein kinase P’s gancyclovir

48
Q

Gancyclovir- most common side effects

A

Bone marrow suppressionCNS effects

49
Q

AZT is an analog of _____. What is the difference?

A

Thymidine 3’ OH group replaced with Azide group (N3)

50
Q

AZT inhibits _____

A

reverse transcriptase

51
Q

AZT isn’t recommended as ___. Why?

A

monotherapy (due to resistance)

52
Q

AZT Sides (3)

A

GranulocytopeniaAnemiaCNS (headache)

53
Q

Cidofovir and Tenofovir work by _____

A

decreasing the amount of HIV in the blood

54
Q

Cidofovir and Tenofovir structure

A

nucleoside analogscontain a PHOSPHATE attached to a SUGAR analog

55
Q

Cidofovir and Tenofovir work independent of _____

A

viral phosphorylation

56
Q

Cidofovir and Tenofovir are substrates for ___ or ____

A

DNA polymerases or RT’s

57
Q

Cidofovir used for _____.SIdes?

A

CMV retinitis in AIDS ptsMay cause LIVER DAMAGE

58
Q

Tenofovir used for

A

HBV and HIV

59
Q

Telbivudine is an nucleoside analog of ___

60
Q

Telbivudine is ____ by _____ enzymes

A

Phosphorylatedcellular Kinase enzymes

61
Q

What form of Telbivudine is its functional form?This inhibits _______

A

Telbivudine-5-TriphosphateHBV DNA polymerase

62
Q

Telbivudine used for

63
Q

Viral polymerase properties (3)

A

NonspecificFast workingProofreading

64
Q

Ribavirin is a _____ that causes ______

A

nucleoside analogerrors in replication and transcription

65
Q

Ribavirin is an analog of _____, but contains ______

A

Guanosinean incomplete (open) ring

66
Q

Ribavirin incorporated into _____The mechanism following this?

A

RNA pairs with URACIL or CYTOSINEinduces mutations in RNA viruses

67
Q

Ribavirin active against…(Try to name all 8)

A

BROAD range of DNA virusesFlavi + ParamyxBunya + ArenaRetro + HerpesAdeno + Pox

68
Q

Ribavirin mode of administration

A

aerosol or oral

69
Q

Ribavirin major toxicity

70
Q

Ribavirin Indication…

A

Aerosol treatment of RSV in kids

71
Q

TFT is a ____ analog. Mechanism?

A

ThymidineCF3 group added o the uracil – BLOCKS base pairing

72
Q

TFT becomes….

A

Phosphorylated by cellular enzymes

73
Q

TFT drug form

A

Ophthalmic solution

74
Q

TFT used for Tx of ____ caused by _____

A

topical Tx of EPITHELIAL KERATITIS caused by HERPESVIRUS

75
Q

Idoxuridine substitutes for ___. Mechanism?

A

ThymidineThe iodine blocks base pairing

76
Q

Idoxuridine used for…

A

HSV Keratoconjunctivitis and Keratitis

77
Q

Idoxuridine phosphorylated by

A

Thymidine Kinase

78
Q

Foscarnet is a ______ resembling ______

A

non nucleoside analogPyrophosphate

79
Q

Foscarnet binds to

A

DNApol (at the pyrophosphate binding site)

80
Q

Foscarnet used for … (3)

A

HerpesvirusHIV Reverse TranscriptaseCMV retinitis in AIDS patients

81
Q

Other NonNS Analogs

A

NevirapineEfavirenzDelavirdine

82
Q

Nevirapine, Efavirenz, Delavirdine are considered _____

A

non-NS Reverse Transcriptase Inhibitors

83
Q

Nevirapine, Efavirenz, Delavirdine mechanism of action

A

Bind RT directlyDisrupt DNApol catalytic siteBlock DNA pol activity *both RNA and DNA dependent*

84
Q

Nevirapine, Efavirenz, Delavirdine doesn;t require…

A

Phosphorylation by cellular enzymes

85
Q

Nevirapine, Efavirenz, Delavirdine – used for

A

HIV-1(HIV2 has different structure RT)

86
Q

Nevirapine, Efavirenz, Delavirdine — used as part of ______

87
Q

Raltegravir is a _______.Blocks ______.

A

Integrase Inhibitorblocks viral DNA integration

88
Q

Interferon is a ______ that functions as a _____

A

Glycoprotein (cytokine)Protein synthesis inhibitor

89
Q

Type 1 Interferons

A

Alpha and Beta

90
Q

IFN alpha has ____ subtypes, and is made by what types of (viral infected) cells?

A

20 subtypesB cellMonocyteMQImmature DC’s

91
Q

IFN Beta has ____ subtypes, and is made by _____

A

2, Fibroblasts

92
Q

IFN alpha aka _____

A

Leukocyte Interferon

93
Q

IFN Beta aka _____

A

Fibroblast Interferon

94
Q

Type 2 Interferonsaka..

A

GammaImmune interferon

95
Q

IFN Gamma number of subtypes? Made by what cells?

A

3Activated T lymphocytes

96
Q

Induction of Interferon (three things)

A

-dsRNA-interaction between sense / antisense mRNA-Interaction of some enveloped viruses

97
Q

Three steps for Interferon mechanism

A
  1. Infected cell releases interferon2. Binds a CSR on another cell3. Induces “antiviral state”
98
Q

Effects of Interferon (2)

A

mRNA DEGRADED (protein synth inhibited)INHIBITS ribosome assembly

99
Q

Interferon inhibits ribosome assembly via

A

EIF-2alpha *initiation factor

100
Q

Interferon produced in response to infection does not affect __________

A

The INITIALLY infected cell

101
Q

Interferon receptor induces what three things in affected cell?

A

2,5 oligoA synthaseRibonuclease LA protein Kinase

102
Q

What is the function of 2,5 OligoA?

A

Activation of Ribonuclease L

103
Q

Interferon has ___ activity

A

Broad spectrum

104
Q

DNA viruses affected by interferon

A

HSV1+2Herpes ZosterhPV

105
Q

RNA viruses affected by interferon

A

InfluenzaChronic HepatitisRhinovirus

106
Q

Other stuf (not DNA or RNA virus) affected by interferon

A

Breast + Lung cancerKaposi Sarcoma

107
Q

Interferon is not ________ bioavailable. Routes?

A

orally*IM, SubQ, Topical

108
Q

Antiviral agents affecting enzymatic functions of viral proteins (2 groups)

A

Protease InhibitorsNeuraminidase Inhibitors (Viral release inhibitors)

109
Q

Protease Inhibitors (6)

A

“BRINTS”Boceprevrin, Ritonavir, Nelfinavir, Indinavir, Tipranavir, Saquinavir

110
Q

Protease inhibitors especially effective against ____ and ___

111
Q

Main mechanism behind protease inhibitors

A

stop cleavage of polyproteins so they cant be used for viral assembly

112
Q

Protease inhibitors not recommended as ____

A

monotherapy

113
Q

Neuraminidase inhibitors (2)

A

Zanamivir Oseltamavir (O shit my Tamiflu doesn’t work)

114
Q

NA inhibitors treat A, B, or both?

115
Q

Neuraminidase functions by catalyzing….

A

cleavage of Sialic Acid (attached to glycoproteins)

Virology (15 decks)

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