Lecture 8: Anti-Hepatitis Agents

Question 1

_____: Inflammatory condition of the liver that often leads to hepatic damage through programmed cell death, apoptosis, or necrosis

Answer 1

Hepatitis

Question 2

True or False: Chronic hepatitis could just be carrier state with or without necrosis

Answer 2

True

Question 3

Chronic Hepatitis is mostly caused by ____ and ___ virus

Answer 3

Hep B and Hep C

Question 4

True or False: Hep B Virus is a single stranded RNA virus while Hep C virus is a DNA virus

Answer 4

False - Hep B is double stranded, DNA virus; Hep C is a RNA virus

Question 5

The life cycle of a Hep B virus involves synthesis of RNA with resultant generation of DNA using the process of _________

Answer 5

Reverse transcription

Question 6

____: The enzyme involved in the process of reverse transcription (as seen in Hep B Virus)

Answer 6

Reverse transcriptase

Question 7

True or False: Hep B multiplication involves RNA replication and RNA Polymerase

Answer 7

False - Hep C multiplication involves RNA replication and RNA Polymerase

Question 8

True or False: Reverse Transcription is central to the replication cycle of Hep C Virus

Answer 8

False - it is NOT!

Question 9

True or False: The treatment of Hep B Virus (HBV) infections are more suppressive rather than curative, whereas for Hep C Virus, it is viral eradication

Answer 9

True

Question 10

Why is therapy for Hep B Virus challenging?

Answer 10

Covalently closed circular DNA (cccDNA) can remain stable inside of cell for a long time

Question 11

Which two interferons can treat Hep B Virus?

Answer 11

1. Recombinant Interferon alpha (IFN-a)
2. PEGylated IFNa

Question 12

Adefovir Dipivoxil and Tenofovir Disoproxil are _____ that treat Hep B Virus
A. Interferons
B. Nucleotide Analogs
C. Nucleoside Analogs

Answer 12

B. Nucleotide Analogs

Question 13

Entecavir, Lamivudine, and Telbivudine are ______ that treat Hep B Virus:
A. Interferons
B. NucleoTIDE Analogs
C. NucleoSIDE Analogs

Answer 13

C. NucleoSIDE Analogs

Question 14

True or False: Interferons (IFN-alpha and Pegylated IFN-alpha) are common agent for treatment of Hep B and Hep C

Answer 14

True

Question 15

What is the benefit of having a pegylated form of IFN-alpha?

Answer 15

LESS of an autoimmune response compared to INF-alpha

Question 16

Interferons act to stimulate ____ signaling pathway

Answer 16

JAK-STAT

Question 17

True or False: Pegylated IFN are generated better tolerated than recombinant non-pegylated IFN’s, showing less auto-immune trigger

Answer 17

True

Question 18

Adefovir and Tenefovir are acyclic nucleotide analogs of ____

Answer 18

AMP (adenosine monophosphate)

Question 19

Once Adefovir dipivocil and Tenefovir disoproxil enters the cell, it is de-esterified to ____/_____

Answer 19

Adefovir and Tenefovir

Question 20

True or False: The monophosphate form of Adefovir/Tenefovir acts as a competitive inhibit for:
1) Viral DNAP
2) Reverse transcriptase
3) Chain termination of viral DNA synthesis

Answer 20

False - the DIPHOSPHATE form does this…

Question 21

Which two molecules can be inhibited by the diphosphate form of Adefovir and Tenefovir?

Answer 21

1) Viral DNAP
2) Reverse transcriptase activity

Leads to: chain termination of viral DNA synthesis

Question 22

True or False: If there is a molecule in the relaxed, closed DNA state, Adefovir/Tenefovir cannot act on it

Answer 22

True

Question 23

True or False: High IV administration of Adefovir has been associated with maternal toxicity, nephrotox, embryotox, fetal malformation

Answer 23

True

Question 24

____: A guanosine analog that has to undergo intracellular phosphorylation to Entecavir triphosphate

Answer 24

Entecavir

Question 25

If one uses entecavir, the formed triphosphate competes with endogenous deoxyguanosine triphosphate and, as a result, inhibits which three processes?

Answer 25

1. Base priming 2. Reverse transcription from RNA 3. Synthesis of positive strand of HBV DNA

Question 26

What are the two major AE associated with Entecavir, a nucleoside analog?

Answer 26

1. Lactic acidosis 2. Severe hepatomegaly

Question 27

What are two features that Lamivudine and Telbivudine have in common?

Answer 27

Both are 1. nucleosides 2. have to be converted by cellular kinases to active, triphosphate form

Question 28

____ is a deoxycytidine analog (nucleotide) which then gets converted to triphosphate form ____ is a thymidine analog, which gets converted to triphosphate form

Answer 28

Lamivudine Telbivudine

Question 29

Lamivudine triphosphate and Telbivudine triphosphate competes with endogenous ______ and _______, respectively, for DNAP enzyme of Hep B Virus. What is the effect of this?

Answer 29

deoxycytidine triphosphate deoxythymidine triphosphate Effect: Hep B Virus DNA Termination

Question 30

True or False: Lamivudine and Telbivudine inhibit reverse transcription and strand synthesis

Answer 30

True

Question 31

___ is a purine nucleoside analog use to treat Hep C Virus A. Lamivudine B. Telbivudine C. Entecavir D. Ribavirin

Answer 31

D. Ribavirin

Question 32

Ribavirin (RBV-monophosphate) competitively inhibits cellular _____, leading to decreased GTP and nucleic acid synthesis

Answer 32

Inosine 5 phosphate dehydrogenase

Question 33

How does RBV triphosphate lead to less infective virions? Prevent replication?

Answer 33

Leads to less infective virions = promotes hypermutagenesis Prevents replication = competitively inhibits GTP-5' capping of viral RNA

Question 34

True or False: Anemia is an AE associated with Ribavirin, as well as elevated serum Fe, bilirubin, and uric acid concentrations

Answer 34

True

Question 35

Which two Hep C Virus proteins have cleavage activity? A. NS5B and NSA5A B. NS5A, NS4A D. NS3, NS4A

Answer 35

D. NS3, NS4A

Question 36

Which Hep C Virus polypeptide protein forms membranous web and is involved in replication and virus assembly? A. NS3 B. NS4A C. NS4B D. NS5A E. NS5B

Answer 36

D. NS5A

Question 37

Which Hep C Virus Polypeptide protein is RNA dependent and functions with RNAP? A. NS3 B. NS4A C. NS4B D. NS5A E. NS5B

Answer 37

E. NS5B

Question 38

Which of the following TWO drugs are first generation NS3/4A Protease Inhibitors? A. Boceprevir B. Glecaprevir C. Simeprevir D. Paritaprevir E. Telaprevir

Answer 38

A. Boceprevir E. Telaprevir

Question 39

True or False: Simeprevir, Paritaprevir, Voxilaprevir, and Glecapreir are second generation NS3/4A Protease Inhibitors and have LESS side effects

Answer 39

True

Question 40

True or False: NS3 and 4A, as well as NS4B, NS5A, and NS5B are all structural proteins

Answer 40

False - all non-structural proteins

Question 41

______ prevents the NS3/4A mediated polyprotein cleavage

Answer 41

NS3/4A Protease Inhibitors

Question 42

Which four drugs are NS5A inhibitors?

Answer 42

Ledipasvir Ombitasvir Velpatasvir Daclatasvir

Question 43

NSA5 is a phosphoprotein that contains domains 1, 2, and 3. What are domains 1 and 2 involved in? Domain 3?

Answer 43

Domain 1 and 2: RNA replication Domain 3: Virion assembly

Question 44

On binding to ___, the inhibitors cause a conformational change, thus forming a barrier for ____ interaction with cellular proteins and membrane residing proteins. As a result virus web formation and RNA replication are ____

Answer 44

NSA5; hindered

Question 45

NS5A inhibitors block replication of ___ RNA Synthesis and assembly of ___

Answer 45

HCV; the virus

Question 46

Which class of drug do Dasabuvir and Sofosbuvir belong to? A. NS5B Inhibitors B. NS5A Inhibitors C. Nucleoside Analog D. Direct NS3/4A Protease Inhibitors

Answer 46

A. NS5B Inhibitors

Question 47

____: an RNA dependent RNAP, which regulates viral RNA genome to produce daughter copies of genetic material A. NS3 B. NS4A C. NS4B D. NS5A E. NS5B

Answer 47

E. NS5B

Question 48

True or False: In all the HCV genotypes, the RNA dependent RNA polymerase structure is fully conserved

Answer 48

True

Question 49

____ is a uridine triphosphate analog that undergoes phosphorylation inside hepatic cell to triphosphate form, which then competes w endogenous nucleotide substrates that get incorporated into nascent RNA chain A. Dasabuvir B. Sofosbuvir

Answer 49

B. Sofosbuvir

Question 50

True or False: Sofosbuvir leads to chain termination and prevents viral RNA replication

Answer 50

True

Question 51

____ interacts with RNA-dependent-RNA-Polymerases at one of the four non-catalytic allosteric binding sites, inhibiting the RNAP activity A. Sofosbuvir B. Dasabuvir

Answer 51

B. Dasabuvir