Lecture 3 - Antivirals Flashcards Preview

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Flashcards in Lecture 3 - Antivirals Deck (115):
1

Three types of host defense against virus

Specific barriersNonspecific cellular barrierimmune system

2

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

chemically deactivated virusesAntibodies

3

Antiviral drugs generally inhibit ______ or _______

ReplicationAttachment

4

Nonspecific defenses (1st and 2nd lines)

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

5

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

ImmunityLymphocytes and AB's

6

Three types of vaccines

InactivatedAttenuatedEngineered

7

Inactivated vaccine has destroyed _____, and intact ______

genomecapsid

8

____ is an inactivated vaccine

Polio

9

Attenuated vaccine replicates ______. Examples are _____ and _____

SlowlyChickenpox, MMR

10

Engineered vaccines have ____ that are produced by ________

viral proteinsyeast cells

11

Example of genetically engineered vaccine

Hep B

12

Why do we need antivirals? (6 reasons)

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

13

Antivirals -- barriers to making effective ones? (6)

Selective toxicityResistanceIntracellular bugsDelay of SymptomsLatent phase hard to targetLimited drug development

14

Successful drug intereferes with either...

Viral functionCell function that virus needs

15

There are antivirals against which viruses?

HSV, VZV, CMVHIVInfluenza A + BHep B + C

16

Six targets for antivirals (steps)

Before attachmentAttachmentPenetration/uncoatingReplication of genomeProtein synthesisAssembly/release

17

Viral disruption is effective against ______ viruses

enveloped

18

Nonoxynol (N9) is a ______ against ___ and ____

DetergentHSV, HIV

19

Citric acid disrupts...

rhinovirus

20

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

21

Maraviroc is a _______. What is its mechanism?

CCR antagonistChanges CCR5 shape so it cant bind gp120

22

Viral attachment blockers have three groups, which are...

Neutralizing antibodiesReceptor antagonistsFusion inhibitors

23

Fusion inhibitor example and general mechanism.

enfuvirtidestop HIV entry to CD4 cells

24

Enfuvirtide mimics...

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

25

Uncoating blocker example (group and 2 examples)

Adamantanes--amantadine--rimantadine

26

Amantadine is a _______ that targets ______. This disrupts _______

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

27

Amantadine is effective against....

Influenza ANOT B

28

Amantadine may cause ______ due to _______

HallucinationDopaminergic action

29

Nucleic Acid Synthesis blocked by ___ and ____

Nucleoside anaolgsNon-Nucleoside analogues

30

Nucleoside analogs inhibit _____.

VIral polymeraseCauses chain termination

31

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

Acyclovir, gancyclovirAZTCidofovir/TenofovirTelbivudine

32

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

errors in replication and transcriptionRibavirinTFTIdoxuridine

33

Non nucleoside analog examples

FoscarnetNevirapine

34

Nucleoside analog mechanism

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

35

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

DNA and RNA pol....Incorporated into DNA

36

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

N3 (azide) group instead of OH

37

Valacyclovir is...

soluble, has better availability

38

Penciclovir form:

cream

39

Famciclovir form:

Oral

40

Acyclovir Tx for

HSV 1 and 2

41

Acyclovir can be thought of as a ______

purine mimic

42

Acyclovir inhibits ______

Viral DNApol 100X AFFINITY

43

Acyclovir activated by

Thymidine kinasesViralHostHost

44

Acyclovir has ____ oral absorption rate

15-30%

45

Gancyclovir is a synthetic analog of _______

2'-deoxy-guanosine

46

Gancyclovir used for

CMV--- retinitisPneumoniaColitis

47

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

Thymidine KinaseCMV encoded protein kinase P's gancyclovir

48

Gancyclovir- most common side effects

Bone marrow suppressionCNS effects

49

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

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

50

AZT inhibits _____

reverse transcriptase

51

AZT isn't recommended as ___. Why?

monotherapy (due to resistance)

52

AZT Sides (3)

GranulocytopeniaAnemiaCNS (headache)

53

Cidofovir and Tenofovir work by _____

decreasing the amount of HIV in the blood

54

Cidofovir and Tenofovir structure

nucleoside analogscontain a PHOSPHATE attached to a SUGAR analog

55

Cidofovir and Tenofovir work independent of _____

viral phosphorylation

56

Cidofovir and Tenofovir are substrates for ___ or ____

DNA polymerases or RT's

57

Cidofovir used for _____.SIdes?

CMV retinitis in AIDS ptsMay cause LIVER DAMAGE

58

Tenofovir used for

HBV and HIV

59

Telbivudine is an nucleoside analog of ___

Thymidine

60

Telbivudine is ____ by _____ enzymes

Phosphorylatedcellular Kinase enzymes

61

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

Telbivudine-5-TriphosphateHBV DNA polymerase

62

Telbivudine used for

HBV

63

Viral polymerase properties (3)

NonspecificFast workingProofreading

64

Ribavirin is a _____ that causes ______

nucleoside analogerrors in replication and transcription

65

Ribavirin is an analog of _____, but contains ______

Guanosinean incomplete (open) ring

66

Ribavirin incorporated into _____The mechanism following this?

RNA pairs with URACIL or CYTOSINEinduces mutations in RNA viruses

67

Ribavirin active against...(Try to name all 8)

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

68

Ribavirin mode of administration

aerosol or oral

69

Ribavirin major toxicity

Anemia

70

Ribavirin Indication...

Aerosol treatment of RSV in kids

71

TFT is a ____ analog. Mechanism?

ThymidineCF3 group added o the uracil -- BLOCKS base pairing

72

TFT becomes....

Phosphorylated by cellular enzymes

73

TFT drug form

Ophthalmic solution

74

TFT used for Tx of ____ caused by _____

topical Tx of EPITHELIAL KERATITIS caused by HERPESVIRUS

75

Idoxuridine substitutes for ___. Mechanism?

ThymidineThe iodine blocks base pairing

76

Idoxuridine used for...

HSV Keratoconjunctivitis and Keratitis

77

Idoxuridine phosphorylated by

Thymidine Kinase

78

Foscarnet is a ______ resembling ______

non nucleoside analogPyrophosphate

79

Foscarnet binds to

DNApol (at the pyrophosphate binding site)

80

Foscarnet used for ... (3)

HerpesvirusHIV Reverse TranscriptaseCMV retinitis in AIDS patients

81

Other NonNS Analogs

NevirapineEfavirenzDelavirdine

82

Nevirapine, Efavirenz, Delavirdine are considered _____

non-NS Reverse Transcriptase Inhibitors

83

Nevirapine, Efavirenz, Delavirdine mechanism of action

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

84

Nevirapine, Efavirenz, Delavirdine doesn;t require...

Phosphorylation by cellular enzymes

85

Nevirapine, Efavirenz, Delavirdine -- used for

HIV-1(HIV2 has different structure RT)

86

Nevirapine, Efavirenz, Delavirdine --- used as part of ______

HAART

87

Raltegravir is a _______.Blocks ______.

Integrase Inhibitorblocks viral DNA integration

88

Interferon is a ______ that functions as a _____

Glycoprotein (cytokine)Protein synthesis inhibitor

89

Type 1 Interferons

Alpha and Beta

90

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

20 subtypesB cellMonocyteMQImmature DC's

91

IFN Beta has ____ subtypes, and is made by _____

2, Fibroblasts

92

IFN alpha aka _____

Leukocyte Interferon

93

IFN Beta aka _____

Fibroblast Interferon

94

Type 2 Interferonsaka..

GammaImmune interferon

95

IFN Gamma number of subtypes? Made by what cells?

3Activated T lymphocytes

96

Induction of Interferon (three things)

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

97

Three steps for Interferon mechanism

1. Infected cell releases interferon2. Binds a CSR on another cell3. Induces "antiviral state"

98

Effects of Interferon (2)

mRNA DEGRADED (protein synth inhibited)INHIBITS ribosome assembly

99

Interferon inhibits ribosome assembly via

EIF-2alpha *initiation factor

100

Interferon produced in response to infection does not affect __________

The INITIALLY infected cell

101

Interferon receptor induces what three things in affected cell?

2,5 oligoA synthaseRibonuclease LA protein Kinase

102

What is the function of 2,5 OligoA?

Activation of Ribonuclease L

103

Interferon has ___ activity

Broad spectrum

104

DNA viruses affected by interferon

HSV1+2Herpes ZosterhPV

105

RNA viruses affected by interferon

InfluenzaChronic HepatitisRhinovirus

106

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

Breast + Lung cancerKaposi Sarcoma

107

Interferon is not ________ bioavailable. Routes?

orally*IM, SubQ, Topical

108

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

Protease InhibitorsNeuraminidase Inhibitors (Viral release inhibitors)

109

Protease Inhibitors (6)

"BRINTS"Boceprevrin, Ritonavir, Nelfinavir, Indinavir, Tipranavir, Saquinavir

110

Protease inhibitors especially effective against ____ and ___

HIVHep C

111

Main mechanism behind protease inhibitors

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

112

Protease inhibitors not recommended as ____

monotherapy

113

Neuraminidase inhibitors (2)

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

114

NA inhibitors treat A, B, or both?

Both!

115

Neuraminidase functions by catalyzing....

cleavage of Sialic Acid (attached to glycoproteins)