Lecture 8: Anti-Hepatitis Agents Flashcards
_____: Inflammatory condition of the liver that often leads to hepatic damage through programmed cell death, apoptosis, or necrosis
Hepatitis
True or False: Chronic hepatitis could just be carrier state with or without necrosis
True
Chronic Hepatitis is mostly caused by ____ and ___ virus
Hep B and Hep C
True or False: Hep B Virus is a single stranded RNA virus while Hep C virus is a DNA virus
False - Hep B is double stranded, DNA virus; Hep C is a RNA virus
The life cycle of a Hep B virus involves synthesis of RNA with resultant generation of DNA using the process of _________
Reverse transcription
____: The enzyme involved in the process of reverse transcription (as seen in Hep B Virus)
Reverse transcriptase
True or False: Hep B multiplication involves RNA replication and RNA Polymerase
False - Hep C multiplication involves RNA replication and RNA Polymerase
True or False: Reverse Transcription is central to the replication cycle of Hep C Virus
False - it is NOT!
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
True
Why is therapy for Hep B Virus challenging?
Covalently closed circular DNA (cccDNA) can remain stable inside of cell for a long time
Which two interferons can treat Hep B Virus?
- Recombinant Interferon alpha (IFN-a)
- PEGylated IFNa
Adefovir Dipivoxil and Tenofovir Disoproxil are _____ that treat Hep B Virus
A. Interferons
B. Nucleotide Analogs
C. Nucleoside Analogs
B. Nucleotide Analogs
Entecavir, Lamivudine, and Telbivudine are ______ that treat Hep B Virus:
A. Interferons
B. NucleoTIDE Analogs
C. NucleoSIDE Analogs
C. NucleoSIDE Analogs
True or False: Interferons (IFN-alpha and Pegylated IFN-alpha) are common agent for treatment of Hep B and Hep C
True
What is the benefit of having a pegylated form of IFN-alpha?
LESS of an autoimmune response compared to INF-alpha
Interferons act to stimulate ____ signaling pathway
JAK-STAT
True or False: Pegylated IFN are generated better tolerated than recombinant non-pegylated IFN’s, showing less auto-immune trigger
True
Adefovir and Tenefovir are acyclic nucleotide analogs of ____
AMP (adenosine monophosphate)
Once Adefovir dipivocil and Tenefovir disoproxil enters the cell, it is de-esterified to ____/_____
Adefovir and Tenefovir
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
False - the DIPHOSPHATE form does this…
Which two molecules can be inhibited by the diphosphate form of Adefovir and Tenefovir?
1) Viral DNAP
2) Reverse transcriptase activity
Leads to: chain termination of viral DNA synthesis
True or False: If there is a molecule in the relaxed, closed DNA state, Adefovir/Tenefovir cannot act on it
True
True or False: High IV administration of Adefovir has been associated with maternal toxicity, nephrotox, embryotox, fetal malformation
True
____: A guanosine analog that has to undergo intracellular phosphorylation to Entecavir triphosphate
Entecavir
If one uses entecavir, the formed triphosphate competes with endogenous deoxyguanosine triphosphate and, as a result, inhibits which three processes?
- Base priming
- Reverse transcription from RNA
- Synthesis of positive strand of HBV DNA
What are the two major AE associated with Entecavir, a nucleoside analog?
- Lactic acidosis
- Severe hepatomegaly
What are two features that Lamivudine and Telbivudine have in common?
Both are
1. nucleosides
2. have to be converted by cellular kinases to active, triphosphate form
____ is a deoxycytidine analog (nucleotide) which then gets converted to triphosphate form
____ is a thymidine analog, which gets converted to triphosphate form
Lamivudine
Telbivudine
Lamivudine triphosphate and Telbivudine triphosphate competes with endogenous ______ and _______, respectively, for DNAP enzyme of Hep B Virus.
What is the effect of this?
deoxycytidine triphosphate
deoxythymidine triphosphate
Effect: Hep B Virus DNA Termination
True or False: Lamivudine and Telbivudine inhibit reverse transcription and strand synthesis
True
___ is a purine nucleoside analog use to treat Hep C Virus
A. Lamivudine
B. Telbivudine
C. Entecavir
D. Ribavirin
D. Ribavirin
Ribavirin (RBV-monophosphate) competitively inhibits cellular _____, leading to decreased GTP and nucleic acid synthesis
Inosine 5 phosphate dehydrogenase
How does RBV triphosphate lead to less infective virions? Prevent replication?
Leads to less infective virions = promotes hypermutagenesis
Prevents replication = competitively inhibits GTP-5’ capping of viral RNA
True or False: Anemia is an AE associated with Ribavirin, as well as elevated serum Fe, bilirubin, and uric acid concentrations
True
Which two Hep C Virus proteins have cleavage activity?
A. NS5B and NSA5A
B. NS5A, NS4A
D. NS3, NS4A
D. NS3, NS4A
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
D. NS5A
Which Hep C Virus Polypeptide protein is RNA dependent and functions with RNAP?
A. NS3
B. NS4A
C. NS4B
D. NS5A
E. NS5B
E. NS5B
Which of the following TWO drugs are first generation NS3/4A Protease Inhibitors?
A. Boceprevir
B. Glecaprevir
C. Simeprevir
D. Paritaprevir
E. Telaprevir
A. Boceprevir
E. Telaprevir
True or False: Simeprevir, Paritaprevir, Voxilaprevir, and Glecapreir are second generation NS3/4A Protease Inhibitors and have LESS side effects
True
True or False: NS3 and 4A, as well as NS4B, NS5A, and NS5B are all structural proteins
False - all non-structural proteins
______ prevents the NS3/4A mediated polyprotein cleavage
NS3/4A Protease Inhibitors
Which four drugs are NS5A inhibitors?
Ledipasvir
Ombitasvir
Velpatasvir
Daclatasvir
NSA5 is a phosphoprotein that contains domains 1, 2, and 3. What are domains 1 and 2 involved in? Domain 3?
Domain 1 and 2: RNA replication
Domain 3: Virion assembly
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 ____
NSA5; hindered
NS5A inhibitors block replication of ___ RNA Synthesis and assembly of ___
HCV; the virus
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
A. NS5B Inhibitors
____: 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
E. NS5B
True or False: In all the HCV genotypes, the RNA dependent RNA polymerase structure is fully conserved
True
____ 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
B. Sofosbuvir
True or False: Sofosbuvir leads to chain termination and prevents viral RNA replication
True
____ interacts with RNA-dependent-RNA-Polymerases at one of the four non-catalytic allosteric binding sites, inhibiting the RNAP activity
A. Sofosbuvir
B. Dasabuvir
B. Dasabuvir
