Antivirals and Diagnostic Virology

Question 1

List the 3 classes of drugs for Influenza antivirals

Answer 1

1. Uncoating
2. Neuraminidase
3. Cap-dependent Endonuclease inhibitor

Question 2

Describe uncoating

Answer 2

Rimantadine/Amantadine blocks uncoating, can only be used on Influenza A, and all current strains are resistant

Question 3

Describe Neuraminidase inhibitors

Answer 3

Blocks the release of the virus by blocking the viral neuraminidase. The most common is Tamiflu

Question 4

Describe cap-dependent Endonuclease inhibitor

Answer 4

Xofluza prevents the virus from taking cellular mRNA caps and using them to make viral mRNA. As a result, viral RNA cant’t be transcribed into mRNA, and viral proteins are not made

Question 5

Describe the antiviral Ribavirin

Answer 5

1. Not specific for one virus and can be used on respiratory syncytial virus, hepatitis C virus, and hemorrhagic fever viruses
2. Ribavirin works by lowering guanine nucleotides in the cell, making replication harder
3. Ribavirin is a teratogen. Two forms of birth control should be used while taking ribavirin and continued for six months after use

Question 6

What steps in HIV replication are inhibited by antivirals?

Answer 6

1) Entry inhibitors block receptor/co-receptor binding or membrane fusion and entry
2) Reverse transcriptase inhibitors, 2 classes:
-Nucleoside Reverse Transcriptase Inhibitors (NRTI)-chain terminators prevent the chain from being elongated
-Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)-bing to reverse transcriptase and prevents its ability to make DNA
-Both block the ability of the virus to make a DNA copy of itself
3) Integrase Inhibitors prevent the virus from inserting the viral DNA into the cellular DNA
4) Protease Inhibitors block the maturation of the viral particle

Question 7

What are the 3 classes of HCV drugs?

Answer 7

1) Viral protease inhibitors block the cleavage of the polyprotein and stop replication after this step. The virus cannot replicate its genetic material
2) Viral RNA-dependent RNA polymerase inhibitors block the ability of the virus to replicate its RNA
3) NS5A inhibitors block RNA production and assembly

Question 8

In regards to Herpesviruses, Acyclovir compounds block the viral polymerase and interfere with viral DNA production. What do they all need to by activated by?

Answer 8

A viral thymidine kinase

This means that the acyclovirs will be preferentially activated in an infected cell that has the viral thymidine kinase

Question 9

When referring to Herpesviruses, what is Acyclovir/Valacyclovir?

Answer 9

Valacyclovir is a prodrug of acyclovir. It is converted to acyclovir in the
body and requires less dosing than acyclovir. Both treat HSV and VZV herpesviruses.

Question 10

When referring to Herpesviruses, what is Famciclovir and Penciclovir?

Answer 10

Famciclovir is oral, and Penciclovir is topical. They are the same active compound and can also treat HSV and VZV herpesviruses.

Question 11

When referring to Herpesviruses, what is Valganciclovir and Ganciclovir?

Answer 11

Valganciclovir and Ganciclovir have more side effects and are used to treat the herpesvirus CMV

Question 12

Why is viral diagnostics used?

Answer 12

1. It is usually used to confirm a diagnosis
2. Diagnosing a virus is necessary for prescribing the correct antiviral drugs
3. It can help monitor chronic infections. Is the virus level increasing or decreasing in the body? Is the antiviral tx working?
4. Monitor the prevalence of a virus in the community, i.e. epidemiological monitoring

Question 13

In cytology, viral infections are determined by looking for….

Answer 13

viral inclusion bodies, syncytia, or using detector antibodies for viral proteins

Question 14

Vaccines require large quantities of virus. Any many vaccines are produced in _________

Answer 14

cultured cells

Question 15

Cell culture can be used to diagnose an infection, but __________ are rapidly replacing the need for viral culture

Answer 15

nucleic acid tests

Question 16

What are ELISA or EIA used for?

Answer 16

1) To detect antibodies present in the body against a specific virus
2) *IgM, which would indicate an acute infection
3) *IgG, which could specify an acute, chronic, or past infection
4) Test for the presence of a viral antigen, which indicates active infection
5) *The test is specific for one virus
6) Check for vaccine efficacy
7) All tests can have false positives or false negatives

Question 17

Describe Lateral Flow Assay

Answer 17

1) It is essentially a quick, easy test and is like an ELISA or EIA
2) Can detect presence of viral antigens or antibodies
3) Quick and can be done in minutes
4) Can be done at doctor’s or at home
5) Have to know what virus to test (one virus tested per assay)
6) Test might not pick up the new strain if the virus undergoes antigen drift

Question 18

Describe Nucleic Acid Amplification Tests (NAAT)

Answer 18

1) Very sensitive and can amplify small amounts of starting material
2) Usually pick up an infection if it is present
3) A specialized NAAT can be used to determine the amount of virus in a person. This is often done in chronic infections to see if antiviral tx is working
4) Test done at doctors (in-house) but sent to a lab - means results take several days
5) NAAT tends to be more expensive than lateral flow assays
6) There are nucleic acid amplification tests that can test for several infections at once. These are costly and usually not done unless the person is hospitalized

Question 19

T/F: Most tests are not 100% accurate

Answer 19

True - there can be false positives and false negatives

Question 20

The ________ of the test is how many people with the disease will test positive

Answer 20

sensitivity

If 100 people have been infected with the flu and only 70 of them test positive on the test, then the sensitivity of the test is 70%

Question 21

The _______ of the test is how many people who DO NOT have the disease will test negative

Answer 21

specificity

If 100 people who are not infected with the flu take the test and 5 of them test positive, then the specificity is 95.5%. Remember, you are looking for a number telling you the percentage of people who do not have the disease who test negative

Question 22

When the prevalence of infection is low, testing can have ______

Answer 22

limited utility

Question 23

What are the different classes of inhibitors for HIV?

Answer 23

-Entry inhibitors
-Reverse Transcriptase (NRTI, NNRTI)
-Integrase Inhibitor
-Protease Inhibitors

Question 24

What are the different classes of inhibitors for HCV?

Answer 24

-Protease inhibitors
-RNA Polymerase Inhibitors
-NS5A Inhibitors

Question 25

What is the function of entry inibitors

Answer 25

block receptor/co-receptor binding or membrane fusion and entry

Question 26

What is the function of reverse transcriptase (NRTI and NNRTI)

Answer 26

-(NRTI)-chain terminators prevent the chain from being elongated

-Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)-bing to reverse transcriptase and prevents its ability to make DNA

-Both block the ability of the virus to make a DNA copy of itself

Question 27

What is the function of Integrase inhibitors

Answer 27

prevent the virus from inserting the viral DNA into the cellular DNA

Question 28

What is the function of protease inhibitors

Answer 28

block the cleavage of the polyprotein and stop replication after this step. The virus cannot replicate its genetic material (block the maturation of the viral particle)

Question 29

What is the function of RNA polymerase inhibitors

Answer 29

Viral RNA-dependent RNA polymerase inhibitors block the ability of the virus to replicate its RNA

Question 30

What is the function of NS5A inhibitors

Answer 30

block RNA production and assembly