Lecture 2

Question 1

What are the main three defenses against viruses?

Answer 1

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

Question 2

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

Answer 2

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)

Question 3

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

Answer 3

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

Question 4

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

Answer 4

1. Must not be a crucial function to cell or

2. Only will kill virus-infected cells

Question 5

In regards to antiviral drugs, what is viral disruption?

Answer 5

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

Question 6

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

Answer 6

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

Question 7

In regards to antiviral drugs, what are receptor antagonists?

Answer 7

• Binds to receptors so virus can’t

* Maraviroc is one such agent

Question 8

In regards to antiviral drugs, what are fusion inhibitors?

Answer 8

• Stop enveloped viruses from getting into cell

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

Question 9

• In regards to antiviral drugs, how do drugs that target uncoating work?
• Two examples?

Answer 9

• Stop proton flow which inhibits uncoating

* Amantadine and rimantadine are two examples

Question 10

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

Answer 10

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

Question 11

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

Answer 11

1. Ribavirin
2. Trifluorothymidine
3. Idoxuridine

Question 12

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

Answer 12

1. Foscarnet

2. Nevirapine

Question 13

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

Answer 13

• 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

Question 14

Acyclovir details?

Answer 14

• 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

Question 15

Ganciclovir details?

Answer 15

• 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

Question 16

Azidothymadine details?

Answer 16

• 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

Question 17

• Acyclic nucleoside phosphonate details?
• Two brand names
• What virus does it affect and how?

Answer 17

• Decreases HIV in blood
• Does not need to be phosphorylated
• Works on DNA polymerase or reverse transcriptase
• Cidofovir/Tenofovir

Question 18

Telbivudine details?

Answer 18

• HBV treatment
• Is phosphorylated
• Thymidine nucleoside
• Inhibits DNA polymerase

Question 19

Ribavirin details?

Answer 19

• 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

Question 20

Trifluorothymidine details?

Answer 20

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

Question 21

Idoxuridine details?

Answer 21

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

Question 22

Foscarnet details?

Answer 22

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

Question 23

Nevirapine, Efavirenz, Delavirdine details?

Answer 23

• 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

Question 24

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

Answer 24

Raltegravir

Question 25

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

Answer 25

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

Question 26

What cells make interferon-α (leukocytes interferon)?

Answer 26

* Virus infected cells | * B cells, monocytes, macrophages, immature dendritic ells

Question 27

What cells make interferon-β (fibroblast interferon)?

Answer 27

* Virus infected cells | * Fibroblasts and other cells

Question 28

What cells make interferon-

Answer 28

Activated T lymphocytes

Question 29

What leads to production of interferon?

Answer 29

* 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)

Question 30

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

Answer 30

* Prepares nearby cells for "antiviral" state via a receptor * Synthesis of protein kinase R → mRNA degraded and protein synthesis blocked * Inhibits ribosome activity

Question 31

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

Answer 31

Increase MHCI expression so ↑ recognition by cytotoxic T cells

Question 32

What DNA viruses is interferon effective against?

Answer 32

* Herpes simplex 1 and 2 * Herpes zoster * HPV

Question 33

What RNA viruses is interferon effective against?

Answer 33

* Influenza * Chronic hepatitis * Common cold

Question 34

What cancers is interferon activated against?

Answer 34

* Breast Ca * Lung Ca * Karposi's sacroma (cancer associated with AIDs)

Question 35

What six drugs affect enzymatic function of viral proteins?

Answer 35

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

Question 36

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

Answer 36

* HIV * Hep C * Not indicated as monotherapy

Question 37

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

Answer 37

Prevent cleaving polyproteins to their final proteins for viral assembly

Question 38

Neuraminidase inhibitors block viral release. How does this occur?

Answer 38

* Viral neuraminidase cleaves terminal sialic acids so they can't release from host cell * These drugs inhibit this mechanism

Question 39

What are two common viral neuramindase inhibitors?

Answer 39

* Zanamivir | * Osetamivir (Tamiflu)