Antivirals and Diagnostic Virology

Question 1

For influenza, what are the 3 classes of drugs?

Answer 1

• uncoating
• nueraminidase inhibitors
• cap-dependent endonuclease inhibitor

Question 2

What do uncoating drugs do for influenza?

Answer 2

• rimantadine/amantadine blocks uncoating
• uncoating is what releases virus to infect
• can only be used on influenza A bc all other strains are resistant

Question 3

What do neuraminidase inhibitors do for influenza?

Answer 3

• block release of virus by blocking viral neuraminidase
• most common: Tamiflu (Oseltamivir)

Question 4

What do cap-dependent endonuclease inhibitors do for influenza?

Answer 4

• xofluza (baloxavir carboxyl) prevents virus from taking cellular mRNA caps and using them to make viral mRNA
• as a result= viral RNA can’t be transcribed into mRNA and viral proteins aren’t made

Question 5

What is one of the non-specific drugs that can be used on respiratory syncytial virus, hep c virus, and hemorrhagic fever viruses?

Answer 5

Ribavirin

Question 6

How does the MOA of ribavirin work?

Answer 6

• inhibits inosine monophosphate dehydrogenase which lowers guanine nucleotides in the cell… makes replication harder
• is a teratogen so must use 2 forms of birth control and not get pregnant for 6 months after use

Question 7

What are the different classes of HIV drugs?

Answer 7

• entry inhibitors
• reverse transcriptase inhibitors (NRTI and NNRTI)
• integrase inhibitors
• protease inhibitors

Question 8

How entry inhibitors for HIV work?

Answer 8

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

Question 9

How do the 2 classes of reverse transcriptase inhibitors for HIV work?

Answer 9

• nucleoside reverse transcriptase inhibitors (NRTI): chain terminators prevent chain from being elongated
• non-nucleoside reverse transcriptase inhibitors (NNRTI): bind to reverse transcriptase and prevent its ability to make DNA

both block ability of virus to make a DNA copy of itself

Question 10

How do integrase inhibitors work for HIV?

Answer 10

• prevent virus from inserting the viral DNA into cellular DNA

Question 11

How do protease inhibitors work for HIV?

Answer 11

• block maturation of viral particle

Question 12

How are chronic infections of HIV treated?

Answer 12

with 2 different classes of drugs

Question 13

What are the classes of drugs for HCV?

Answer 13

• protease inhibitors
• RNA polymerase inhibitors
• NS5A inhibitors

Question 14

How do protease inhibitors work for HCV?

Answer 14

• prevent polyprotein cleavage and block replication of RNA because it can’t cleave polyprotein to make an active viral polymerase

Question 15

How do RNA polymerase inhibitors work for HCV?

Answer 15

• blocks ability of virus to replicate its RNA

Question 16

How do NS5A inhibitors work for HCV?

Answer 16

• block RNA production and assembly/release of new viral particles

Question 17

What do all herpesvirus antivirals act on?

Answer 17

viral DNA polymerase (bc DNA virus)
- Acyclovir compounds block viral polymerase and interfere with viral DNA production
- they all need to be activated by a viral thymidine kinase so will be preferentially activated in an infected cell that has the viral thymidine kinase

Question 18

What is Valacyclovir for herpesvirus tx?

Answer 18

• it is a prodrug of acyclovir
• converted to acyclovir in body and requires less doing that acyclovir
• both tx HSV and VZV herpesvirus

Question 19

What is the difference between famiciclovir and penciclovir?

Answer 19

• famciciclovir is oral
• penciclovir is topical
  both same active compound that treat HSV and VZV herpesvirus

Question 20

What are the downsides of valganciclovir and ganciclovir and what do they tx?

Answer 20

• have more side effects
• tx for herpesvirus CMV

Question 21

How do lateral flow assays work?

Answer 21

• detect viral antigens or antibodies
• similar to ELISA. quick and easy
• downside: might not pick up new strain if virus undergoes antigen drift
• done in office or at home

Question 22

How do nucleic acid amplification tests (NAAT) work?

Answer 22

• very sensitive and amplify small amounts of starting material
• usually pick up an infection if present
• specialized NAAT used to determine amount of virus in a person (amount of viral load)
• tests done in lab mostly so have to wait a few days for results… more recently started doing in office
• more expensive than lateral flow assays
• can test for multiple infections at once

Question 23

Why is viral diagnostics important?

Answer 23

• usually used to confirm a diagnosis
• necessary for prescribing correct antiviral drugs
• help monitor chronic infections if it’s increasing/decreasing or if antiviral tx is working
• monitor prevalence of virus in community

Question 23

Where are viruses usually grown for production of viruses?

Answer 23

• cell culture
• vaccines require large quantities of virus

Question 23

How are viral infections determined in cytology?

Answer 23

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

Question 23

What is rapidly replacing the need for cell culture for diagnosis of an infection?

Answer 23

• nucleic acid tests

Question 23

How do antibodies/antigen ELISA (enzyme-linked immunosorbent assay) test work?

Answer 23

• used to detect antibodies present in body against one specific virus
• test can be for IgM: indicates an acute ingection
• test can also be for IgG: indicate acute, chronic, or past infection (chronic because in blood)
• test also to detect presence of a viral antigen: indicates an active infection
• test can help check vaccine efficacy (if antibodies were developed)

Question 24

What is the sensitivity of the test determined by?

Answer 24

• how many people with the disease will test positive

ex: if 100 people who have the virus and only 70 test positive, the sensitivity of the test is 70%

Question 25

What is the specificity of the test determined by?

Answer 25

• how many people who do not have the disease will test negative (false positives)

ex: if 100 people who do not have the virus and 5 people test positive, the specificity of the test is 95%

Question 26

If you have a low prevalence of disease/infection, you have a low ________.

Answer 26

low/limited utility