9.1 Anti-virals

Question 1

Label 1-6 of a virus lifecycle

Answer 1

Question 2

Antiviral drugs shows the best response in which type of patients?

Answer 2

In patients with competent immune systems ➞ a healthy immune system works synergistically with drug to eliminate or suppress viral activity

Question 3

Give 4 DNA viruses treated with anti-viral agents

Answer 3

1. Herpes simplex I & II
2. Varicella-zoster virus
3. Cytomegalovirus
4. Hepatitis B
5. Epstein Barr Virus
6. Human Herpes-virus 8

Question 4

Give 4 RNA viruses treated with anti-viral agents

Answer 4

1. Influenza
2. Human Immunodeficiency Virus (HIV)
3. Hepatitis C
4. Respiratory Syncitial Virus (RSV)

Question 5

Give 2 drugs used to treat Influenza

Answer 5

1. Oseltamivir
2. Zanamivir
3. Amantadine
4. Rimantadine

Question 6

Give 4 Influenza-related complications

Answer 6

1. bronchitis
2. pneumonia
3. sinusitis
4. exacerbation of underlying disease

Question 7

Give the 3 types of Influenza virus and give a feature of each

Answer 7

1) Influenza A: has multiple host species and does antigenic drift and shift
2) Influenza B: has no animal reservoir and lower mortality
3) Influenza C: common cold like flu

Question 8

Give the 3 main surface antigens of Influenza and explain how each causes damage

Answer 8

1) Neuraminidase: glycoprotein that hydrolyses mucus on respiratory epithelia, then digests sialic acid on cell surface. Allows entry and exit of influenz into host cell
2) Hemagglutinin: attachment + membrane fusion with endosome.
3) Matrix 2: viral uncoating which releases viral RNA and proteins

Question 9

Which part of the influenza lifecycle do vaccines target?

Answer 9

Attachement and entering of host cell

Question 10

Give the MoA of M2 ion channel blockers

Answer 10

Blocks the ion channel function of the M2 protein of influenza A virus which Inhibits viral uncoating ➞ interferes with corresponding steps in viral life cycle

Question 11

Give an example of an M2 ion channel blocker and which type of influenza these target

Which drug family do these belong too?

Answer 11

Amantadine and Rimantadine ➞ active against influenza A

Belong to the Tricyclic primary amines class

Question 12

Give an example of a neuraminidase inhibitor

Answer 12

Zanamavir and Oseltamivir

Question 13

Zanamavir is a ________. It has a ______ bioavailability and is detectable in ______ up to 24 hours post dosing. Following metabolism it is excreted ______.

Answer 13

Neuraminidase inhibitors, low, sputum, renally

Question 14

How is Zanamivir administered and what types of influenza does it treat?

Give 2 adverse effects

Answer 14

Given via inhalation

Spectrum: Uncomplicated influenza A and B, some strains of avian influenza, H5N1

Adverse effects: nasal and throat discomfort, bronchospasm

Question 15

What is Oseltamivir and which type of influenza does this treat

Give 2 adverse effects

Answer 15

Oseltamivir is a neuraminidase inhibitor which is a pro-drug and has 80% bioavailability

Spectrum: Infuenza A and B in children and adults, avian influenza and H5N1

Adverse effects: Nausea and vomitting, headache

Question 16

Give the MoA of Oseltamivir

Answer 16

Cleaves terminal sialic acid residues on glycoconjugates and destroys receptors

Newly formed virions adhere to cell surface because they cannot digest sialic acid which limits spread

Question 17

Resistance is emerging against what neuraminidase inhibitor and why?

Which drug are viruses still sensitive too?

Answer 17

Oseltamivir H1N1 resistance due to H274Y mutation around active site

Viruses generally remain zanamivir sensitive

Question 18

Give 2 oral agents again Herpes simplex and Varicella zoster

Answer 18

1. Aciclovir
2. Valaciclovir
3. Famciclovir

Question 19

Give 2 topical agents again Herpes simplex and Varicella zoster

Answer 19

Aciclovir and Penciclovir

Question 20

Aciclovir is uptaken by infected cell where ________ phosphorylates it to acyclovir ________

Cellular enzymes then convert it to acyclovir triphosphate which competes with ________ for viral DNA polymerases

When acyclovir triphosphate incorperates into DNA it results in _________ due to the absence of a ________ group

This prevents attachment of additional nucleosides and Inactivates the viral DNA polymerase

Answer 20

VSTK (virus-specific thymidine kinase), monophosphate, dGTP, chain termination, 3’ hydroxyl

Question 21

What are the 2 types of Herpes virus?

Answer 21

HSV-1: Oral Herpes
HSV-2: Genital Herpes

Question 22

Give 2 consequences of HSV

Answer 22

Herpes encephalitis and Herpes Meningitis

Question 23

What is Mollaret’s meningitis?

Answer 23

Recurrent Herpes Meningitis

Question 24

Giveve 3 ways resistance against Aciclovir may occur

Answer 24

1) reduced or absent thymidine kinase
2) altered thymidine kinase activity resulting in decreased acyclovir phosphorylation
3) altered viral DNA polymerase with decreased affinity for acyclovir triphosphate

Question 25

Give 2 drugs used to treat Cytomegalovirus

Answer 25

1. Ganciclovir 2. Valganciclovir 3. Foscarnet 4. Cidofovir

Question 26

Does CMV always require treatment? Explain your answer

Answer 26

Primary CMV infection rarely requires treatment in immunocompetent host However, in immunocompromised hosts re-activation of CMV can be dangerous hence requires treatment

Question 27

Compare presentation of primary vs reactivated CMV

Answer 27

Primary: usually asymptomatic or flu-like symptoms (usually goes undiagnosed) reactivation: CMV retinitis, CMV colitis, etc...

Question 28

What is ART and explain simply what it does What is HART?

Answer 28

Antiretroviral Treatment- aims to suppress the virus and may help to reverse some damage to the immune system. Acts by halting viral replication at various places throughout the HIV life cycle HART: Highly active antiretroviral therapy

Question 29

What are the 3 main drugs used in ART and what is the "basic recipe"?

Answer 29

1) nucleoside reverse transcriptase inhibitors (NRTI) 2) protease inhibitors 3) Integrase inhibitors Basic recipe = two NRTIs + one drug from a different class

Question 30

Genotypic testing is done when a new diagnosis of viral infection is made, why?

Answer 30

To test for resistance through mutations

Question 31

Give a drug used to treat Hepatitis B

Answer 31

1. Lamivudine 2. Entecavir 3. Interferons

Question 32

Compare the need for treatment of acute Hep B vs chronic Hep B

Answer 32

Acute Hepatitis B rarely requires treatment Chronic Hepatitis B may require treatment

Question 33

Give the MoA of Interferons

Answer 33

Not directly virucidal or virustatic Induces changes in the infected or exposed cell to promote resistance to the virus and Induces several enzyme activities that promote an antiviral state

Question 34

What is SVR in terms of Hep C treatment and how is it defined?

Answer 34

SVR = Sustained virologic response Defined as an undetectable RNA level 12 weeks following the completion of therapy

Question 35

Give 4 targets to promote an anti-viral state

Answer 35

1. Proteins that inhibit synthesis of RNA 2. Proteins that cleave viral DNA 3. Proteins that inhibit mRNA 4. Alterations of the cell membrane that inhibit the release of replicated virions

Question 36

Give a drug used to treat Hepatitis C + a new drug class used in treatment

Answer 36

1. Drug = Ribavirin 2. Pegylated interferon New drug class **➞ Novel DAA’s**

Question 37

What is Ribavirin?

Answer 37

A purine nucleoside analog used in the treatment of Hep C

Question 38

The MoA of Ribavirin is unclear but it is though to do what 4 things?

Answer 38

1. causes alterations to cellular nucleotide pools 2. inhibits viral RNA synthesis 3. lethal mutagenesis of certain RNA viral genomes 4. possibly acts as an analog of guanosine or xanthosine

Question 39

Explain the targets of new DDAs in treatment of Hep C

Answer 39

When inside the cell, viral polyproteins are synthesised on ER and then processed by protease such as **NS3-4A** which cleaves proteins (target for DDAs) 2 of these proteins are also impt targets of DDAs * NS5A which regulates Hep C viral RNA * NS5B which serves as the RNA dependant RNA polymerase

Question 40

Give the 4 classes of DDA's

Answer 40

1. NS3-4A protease inhibitors 2. NS5B nucleoside polymerase inhibitors 3. NS5B non-nucleoside polymerase inhibitors 4. NS5A inhibitors

Question 41

Give 2 advantages of NS3-4A protease inhibitors + an example

Answer 41

low barrier to resistance and high potency varies c genotype Example ➞ Simeprevir

Question 42

Give an example of NS5A inhibitor

Answer 42

Daclatasvir

Question 43

Give an example of NS5B nucleoside polymerase inhibitor + 2 advantages of this

Answer 43

Sofosbuvir Advantages: moderate to high efficacy across all six genotypes and high barrier to resistance

Question 44

Give an example of NS5B nucleoside polymerase inhibitor Give one advantage and one disadvantage of this

Answer 44

Dasabuvir Advantages: low barrier to resistance Disadvantage: potency varies among c genotype

Question 45

Give 2 examples of fixed dose combinations

Answer 45

1. Elbasvir-grazoprevir 2. Glecaprevir-pibrentasvir