Lecture 3 - Antiviral Agents Flashcards
(115 cards)
1
Q
Three types of host defense against virus
A
Specific barriers
Nonspecific cellular barrier
immune system
2
Q
Vaccine based on person exposure to ____ in order to make ______
A
chemically deactivated viruses
Antibodies
3
Q
Antiviral drugs generally inhibit ______ or _______
A
Replication
Attachment
4
Q
Nonspecific defenses (1st and 2nd lines)
A
1st = skin, mucous membrane
2nd = WBC, antimicrobial proteins, inflammation
5
Q
Third line of host defense is based on _____ and consists of _____ and ______
A
Immunity
Lymphocytes and AB’s
6
Q
Three types of vaccines
A
Inactivated
Attenuated
Engineered
7
Q
Inactivated vaccine has destroyed _____, and intact ______
A
genome
capsid
8
Q
____ is an inactivated vaccine
A
Polio
9
Q
Attenuated vaccine replicates ______. Examples are _____ and _____
A
Slowly
Chickenpox, MMR
10
Q
Engineered vaccines have ____ that are produced by ________
A
viral proteins
yeast cells
11
Q
Example of genetically engineered vaccine
A
Hep B
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
13
Q
Antivirals – barriers to making effective ones? (6)
A
Selective toxicity Resistance Intracellular bugs Delay of Symptoms Latent phase hard to target Limited drug development
14
Q
Successful drug intereferes with either…
A
Viral function
Cell function that virus needs
15
Q
There are antivirals against which viruses?
A
HSV, VZV, CMV
HIV
Influenza A + B
Hep B + C
16
Q
Six targets for antivirals (steps)
A
Before attachment Attachment Penetration/uncoating Replication of genome Protein synthesis Assembly/release
17
Q
Viral disruption is effective against ______ viruses
A
enveloped
18
Q
Nonoxynol (N9) is a ______ against ___ and ____
A
Detergent
HSV, HIV
19
Q
Citric acid disrupts…
A
rhinovirus
20
Q
The first group of viral attachment blocking agents rely on _____. This interferes with ____ and causes ______
A
neutralizing antibodies
Interferes with Binding to receptors
Causes aggregation of viral particles
21
Q
Maraviroc is a _______. What is its mechanism?
A
CCR antagonist
Changes CCR5 shape so it cant bind gp120
22
Q
Viral attachment blockers have three groups, which are…
A
Neutralizing antibodies
Receptor antagonists
Fusion inhibitors
23
Q
Fusion inhibitor example and general mechanism.
A
enfuvirtide
stop HIV entry to CD4 cells
24
Q
Enfuvirtide mimics…
A
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 base
M2 protein
Disrupts H2 Transport, which inhibits uncoating of viral genome.
27
Amantadine is effective against....
Influenza A
NOT B
28
Amantadine may cause ______ due to _______
Hallucination
Dopaminergic action
29
Nucleic Acid Synthesis blocked by ___ and ____
Nucleoside anaolgs
Non-Nucleoside analogues
30
Nucleoside analogs inhibit _____.
VIral polymerase
Causes chain termination
31
Nucleoside analogs that target viral Polymerase: examples (4 groups)
Acyclovir, gancyclovir
AZT
Cidofovir/Tenofovir
Telbivudine
32
Nucleoside analogs can also cause ______. Examples? (3)
errors in replication and transcription
Ribavirin
TFT
Idoxuridine
33
Non nucleoside analog examples
Foscarnet
Nevirapine
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 Kinase
CMV encoded protein kinase P's gancyclovir
48
Gancyclovir- most common side effects
Bone marrow suppression
| CNS 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)
Granulocytopenia
Anemia
CNS (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 pts
May cause LIVER DAMAGE
58
Tenofovir used for
HBV and HIV
59
Telbivudine is an nucleoside analog of ___
Thymidine
60
Telbivudine is ____ by _____ enzymes
Phosphorylated
cellular Kinase enzymes
61
What form of Telbivudine is its functional form?This inhibits _______
Telbivudine-5-Triphosphate
HBV DNA polymerase
62
Telbivudine used for
HBV
63
Viral polymerase properties (3)
Nonspecific
Fast working
Proofreading
64
Ribavirin is a _____ that causes ______
nucleoside analog
errors in replication and transcription
65
Ribavirin is an analog of _____, but contains ______
Guanosine
an incomplete (open) ring
66
Ribavirin incorporated into _____The mechanism following this?
RNA pairs with URACIL or CYTOSINE
induces mutations in RNA viruses
67
Ribavirin active against...(Try to name all 8)
BROAD range of DNA viruses
Flavi + Paramyx
Bunya + Arena
Retro + Herpes
Adeno + 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?
Thymidine
CF3 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?
Thymidine
The 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 analog
Pyrophosphate
79
Foscarnet binds to
DNApol (at the pyrophosphate binding site)
80
Foscarnet used for ... (3)
Herpesvirus
HIV Reverse Transcriptase
CMV retinitis in AIDS patients
81
Other NonNS Analogs
Nevirapine
Efavirenz
Delavirdine
82
Nevirapine, Efavirenz, Delavirdine are considered _____
non-NS Reverse Transcriptase Inhibitors
83
Nevirapine, Efavirenz, Delavirdine mechanism of action
Bind RT directly
Disrupt DNApol catalytic site
Block 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 Inhibitor
blocks 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 subtypes
B cell
Monocyte
MQ
Immature 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 interferon
2. Binds a CSR on another cell
3. 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 synthase
Ribonuclease 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+2
Herpes Zoster
hPV
105
RNA viruses affected by interferon
Influenza
Chronic Hepatitis
Rhinovirus
106
Other stuf (not DNA or RNA virus) affected by interferon
Breast + Lung cancer
Kaposi Sarcoma
107
Interferon is not ________ bioavailable. Routes?
orally
*IM, SubQ, Topical
108
Antiviral agents affecting enzymatic functions of viral proteins (2 groups)
Protease Inhibitors
Neuraminidase Inhibitors (Viral release inhibitors)
109
Protease Inhibitors (6)
"BRINTS"
Boceprevrin, Ritonavir, Nelfinavir, Indinavir, Tipranavir, Saquinavir
110
Protease inhibitors especially effective against ____ and ___
HIV
Hep 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)
