Lecture 2 Flashcards

1
Q

What are the main three defenses against viruses?

A
  1. Host defenses
  2. Control (vaccines)
  3. Antiviral drugs
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2
Q

What are the three types of viral vaccines that are available?

A
  1. Inactivated (genome destroyed, capsid intact-polio)
  2. Attenuated (extremely slow release of live virus-pox, MMR)
  3. Genetically engineered (viral proteins produced in yeast cells)
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3
Q

What are the two main aspects that an antiviral drug can target?

A
  1. Specific viral function (like an enzyme needed for viral life cycle)
  2. A cellular function virus needs in order to replicate
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4
Q

If an antiviral drug targets a cellular function that a virus needs to replicate, what are the two main things that must happen?

A
  1. Must not be a crucial function to cell or

2. Only will kill virus-infected cells

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5
Q

In regards to antiviral drugs, what is viral disruption?

A
  • Disrupting enveloped viruses
  • (Nonoxynol-detergent for HSV, HIV)
  • (Citric acid-common cold rhinovirus)
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6
Q

In regards to antiviral drugs, how can they target viral attachment?

A
  • As antibodies that bind to virus
  • Can’t interact with receptors
  • Cause viral particle aggregation
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7
Q

In regards to antiviral drugs, what are receptor antagonists?

A
  • Binds to receptors so virus can’t

* Maraviroc is one such agent

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8
Q

In regards to antiviral drugs, what are fusion inhibitors?

A
  • Stop enveloped viruses from getting into cell

* Important to stop HIV from getting into CD4 (enfuvirtide)

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9
Q
  • In regards to antiviral drugs, how do drugs that target uncoating work?
  • Two examples?
A
  • Stop proton flow which inhibits uncoating

* Amantadine and rimantadine are two examples

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10
Q

What five drugs are nucleoside analogs that inhibit viral polymerase by causing chain termination?

A
  1. Acyclovir
  2. Ganciclovir
  3. Azidothymidine
  4. Acyclic nucleoside phosphonates (cidofovir, tenofovir)
  5. Telbivudine
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11
Q

What three drugs are nucleoside analogs that cause errors in replication and transcription?

A
  1. Ribavirin
  2. Trifluorothymidine
  3. Idoxuridine
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12
Q

What are non-nucleoside analogs that still target nucleic acid synthesis?

A
  1. Foscarnet

2. Nevirapine

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13
Q

What is the general mechanism of action that nucleoside analog drugs use to inhibit nucleic acid synthesis?

A
  • Taken up by cells
  • Converted by viral and cellular enzymes to triphosphate form
  • Triphosphate form inhibits DNA and RNA polymerase
  • Incorporated into growing DNA leading to abnormal proteins and breakage
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14
Q

Acyclovir details?

A
  • Mainly for HSV 1 and 2 treatment
  • Purine mimic
  • 100x affinity for viral DNA polymerase
  • Looks like deoxyguanosine
  • ↓ pain and ↑ healing of sores from chickenpox, h. zoster, and genital herpes
  • Prevent outbreaks of genital herpes
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15
Q

Ganciclovir details?

A
  • Herpes virus, CMV (however CMV does not encode a thymidine kinase)
  • 30x affinity for viral DNA polymerase
  • 2-deoxyy-guanosine analogue
  • Can cause bone marrow suppression and CNS effects
  • Drug of choice for CMV infection: retinitis, pneumonia, colitis
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16
Q

Azidothymadine details?

A
  • HIV treatment (inhibits reverse transcriptase)
  • Thymidine analog
  • 45% granulocytopenia and anemia in AIDS PTs but only 5% if PT is asymptomatic
  • Delays onset of aids
17
Q
  • Acyclic nucleoside phosphonate details?
  • Two brand names
  • What virus does it affect and how?
A
  • Decreases HIV in blood
  • Does not need to be phosphorylated
  • Works on DNA polymerase or reverse transcriptase
  • Cidofovir/Tenofovir
18
Q

Telbivudine details?

A
  • HBV treatment
  • Is phosphorylated
  • Thymidine nucleoside
  • Inhibits DNA polymerase
19
Q

Ribavirin details?

A
  • Active against broad range of RNA and DNA viruses
  • Guanosine analog
  • Drug incorporated into RNA which induces mutations
  • Aerosal or oral administration
  • Can cause anemia
  • For RSV in children
20
Q

Trifluorothymidine details?

A
  • Thymidine analogue
  • Is phosphorylated
  • Ophthalmic solution (epithelial keratitis caused by herpes simplex virus)
21
Q

Idoxuridine details?

A
  • Inhibits viral replication by acting as a thymidine substitute in viral DNA
  • For keratoconjunctivitis and keratitis caused by herpes simplex virus
22
Q

Foscarnet details?

A
  • Resembles pyrophosphate
  • Binds to DNA polymerase and blocks binding
  • Herpes, HIV reverse transcriptase, CMV retinitis in AIDs PTs
23
Q

Nevirapine, Efavirenz, Delavirdine details?

A
  • Bind to reverse transcriptase (blocks RNA dependent and DNA dependent DNA polymerase)
  • Does not require phosphorylation
  • Use in combination with other antiretrovirals for HIV-1 infections
24
Q

Integrase is used to integrate viral DNA into host DNA. What is one drug that acts against integrase?

A

Raltegravir

25
Q

Interferon is a cytokine. What is their main function in regards to viruses?

A
  • Interfere with replication of viruses by inhibiting protein synthesis of infected cells
  • Induced by foreign agents such as viruses, bacteria, and others
26
Q

What cells make interferon-α (leukocytes interferon)?

A
  • Virus infected cells

* B cells, monocytes, macrophages, immature dendritic ells

27
Q

What cells make interferon-β (fibroblast interferon)?

A
  • Virus infected cells

* Fibroblasts and other cells

28
Q

What cells make interferon-

A

Activated T lymphocytes

29
Q

What leads to production of interferon?

A
  • Double stranded RNA
  • Interaction between sense/antisense mRNA for some DNA viruses
  • Interaction of some envelope viruses with dendritic cells (DNA viruses are usually poor inducers)
30
Q

Once a cell releases interferon, what is the molecules main action?

A
  • Prepares nearby cells for “antiviral” state via a receptor
  • Synthesis of protein kinase R → mRNA degraded and protein synthesis blocked
  • Inhibits ribosome activity
31
Q

What is one common function that all three interferon molecules have?

A

Increase MHCI expression so ↑ recognition by cytotoxic T cells

32
Q

What DNA viruses is interferon effective against?

A
  • Herpes simplex 1 and 2
  • Herpes zoster
  • HPV
33
Q

What RNA viruses is interferon effective against?

A
  • Influenza
  • Chronic hepatitis
  • Common cold
34
Q

What cancers is interferon activated against?

A
  • Breast Ca
  • Lung Ca
  • Karposi’s sacroma (cancer associated with AIDs)
35
Q

What six drugs affect enzymatic function of viral proteins?

A
  1. Saquinavir
  2. Indinavir
  3. Nelfinavir
  4. Ritonavir
  5. Tipranavir
  6. Boceprevrin
36
Q

There are drugs that affect the enzymatic function of viral proteins. What diseases indicate the need for this type of therapy?

A
  • HIV
  • Hep C
  • Not indicated as monotherapy
37
Q

There are drugs that affect the enzymatic function of viral proteins. How do they specifically work?

A

Prevent cleaving polyproteins to their final proteins for viral assembly

38
Q

Neuraminidase inhibitors block viral release. How does this occur?

A
  • Viral neuraminidase cleaves terminal sialic acids so they can’t release from host cell
  • These drugs inhibit this mechanism
39
Q

What are two common viral neuramindase inhibitors?

A
  • Zanamivir

* Osetamivir (Tamiflu)