Antiviral Drugs

Question 1

What are 2 “virucidal” virus treatments?

Answer 1

Detergents and Cryotherapy

Question 2

What are three types of virus treatments?

Answer 2

Virucidal, Immunomodulary, antivirals

Question 3

What is an example of immunomodulary virus treatments? What is the goal of the treatment?

Answer 3

Example: Pegylated Interferon
Goal: Stimulate the intrinsic immune system

Question 4

What are 4 classes of antivirals?

Answer 4

1- nucleoside analogs
2- non- nucleosides
3- protease inhibitors
4- entry inhibitors

Question 5

Which antivirials are the most effective?

Answer 5

“Nucs” and “Non nucs”

Question 6

Which type of antivirals are no longer used?

Answer 6

Antivirals inhibiting uncoating of the virus

Question 7

What are the key viral function targets of antivirals?

Answer 7

1- Entry
2- Genome replication
3- Assembly
4- Release from the Cell

Question 8

Why is there a general lack of “broad spectrum” antivirals?

Answer 8

Specificity of antivirals is a problem. Typically antivirals tend to target one function of one virus. Not universal.

Question 9

What can happen when a drug is cleared from an individual’s system? What is done to prevent this?

Answer 9

Viral rebounding. Leads to need for life-long therapy in some cases.

Question 10

Can resistance mutations exist in a patient before drug treatment?

Answer 10

Yes

Question 11

How does antivirals lead to increased drug resistance?

Answer 11

Drug treatment selects for resistant virus strains

Question 12

What are 4 factors leading to emergence of resistant variants?

Answer 12

1- High rate of virus replication
2- High Mutation rate (RNA»DNA)
3- High selective drug pressure
4- Immunosuppression of the host

Question 13

Which of these counters resistnace to antivirals?
1- alleviating immunosuppression in the treated person
2- HAART
3- Targeting host functions

Answer 13

All of them!

Question 14

Why is targeting host functions with antivirals dangerous?

Answer 14

Need to be careful of toxicity. Can be helpful is infected cells have a unique profile that can be a drug target and if virus mutations do not impact cellular genes.

Question 15

What antiviral is used to treat HSV-1, HSV-2, and CZV?

Answer 15

Acyclovir

Question 16

Who should be treated for a HSV-1, HSV-2, or CZV infection?

Answer 16

1- Neonates infected at birth
2- Immunodeficient
3- People with complicated HSV infections
4- People with frequent reoccurences

Question 17

What is the structure of Acyclovir?

Answer 17

Nucleoside analog of guanosine

Question 18

Explain the mechanism of Acyclovir

Answer 18

Phosphorylated once by a viral kinase. Phosphorylated twice more by host kinases. The triphosphate ACV inhibits viral DNA polymerase by competing with G for incorporation into DNA. It is a chain terminator

Question 19

What is the structure of ganciclovir?

Answer 19

nucleoside analog of guanosine

Question 20

What is the problem with ganciclovir treatment?

Answer 20

High toxicity, suppresses the bone marrow, mutagenic and teratogenic

Question 21

What virus is ganciclovir effective in treating?

Answer 21

CMV

Question 22

What are the two “broad spectrum” antivirals for DNA viruses?

Answer 22

Foscarnet and Cidovir

Question 23

How are Foscarsnet and Cidofovir administered?

Answer 23

IV only

Question 24

What viruses is foscarnet effective against?

Answer 24

all the Herpesviruses

Question 25

What viruses is cidofovir effective against?

Answer 25

Herpesviruses, adenoviruses, papillomavirues, poxvirus

Question 26

Where does the most toxicity occur with Foscarnet and Cidofovir?

Answer 26

Kidneys

Question 27

Drugs designed for what, are used to treat HBV?

Answer 27

HCV and HIV

Question 28

For people with HBV, who should be treated?

Answer 28

People with chronic or active HBV disease, people co-infected with HCV and or HIV, people whoare progressing to cirrhosis, liver failure, or hepatocellular carcinoma.

Question 29

What are the antivirals used to treat influenza?

Answer 29

Zanamivir and Oseltamivir

Question 30

What is the main treatment option for people who need treatment for HBV?

Answer 30

PEG-IFN-alpha

Question 31

What is the structure and function of Zanamivir and Oseltamivir?

Answer 31

Sialic acid analogs that inhibit viral neuraminidase. Virions remain attached to the cell.

Question 32

What is the "broad spectrum" RNA antiviral?

Answer 32

Ribavirin

Question 33

What is the structure of ribavirin?

Answer 33

nuceoside analogu of guanosine

Question 34

How is ribavirin formulated?

Answer 34

oral, IV and aerosole

Question 35

What is Ribavirin approved for used against?

Answer 35

HCV and RSV

Question 36

Which antiviral has a lot of off label use?

Answer 36

Ribavirin

Question 37

How is HCV treated?

Answer 37

combined therapy of Peg-interferon-alpha with Ribavirin

Question 38

Problem with HCV therapy?

Answer 38

Not all HCV genotypes respond to drugs

Question 39

Which hepatitis virus has awful treatment side effects?

Answer 39

HCV

Question 40

What are two alternative treatments for HCV? Are they approved yet?

Answer 40

Sofosbuvir and Ledipasvir. They are not approved yet!

Question 41

What are the classes of anti-HIV drugs?

Answer 41

``` 1- Entry inhibitors 2- Nucleoside/tide RT inhibitor 3- Non-nucleoside RT inhibitor 4- Integrase inhibitor 5- Protease inhibitor ```

Question 42

What is critical in HIV treatment?

Answer 42

HAART (using multiple drugs in treatment that target different stages of viral replication) and compliance.

Question 43

What is cobicistat? What are its benefits?

Answer 43

a drug enhancer that inhibits CYP3A4 that breaks down drugs in the liver. Benefit is that it allows for fewer pills or doses.