Midterm #3: Viral Genome Part 2

Question 1

Drug Targets in HIV Lifecyle

Answer 1

• Receptor Binding
• Membrane Fusion
• RT (RNA to DNA)
• DNA integration
• Polyprotein proteolysis

Question 2

HIV has 3 stages of Attachement

Answer 2

• Heparan sulfate for initial adhesion
• CD4 Receptor binding for intial triggering
• Chemokine coreceptor binding for fusion inititation
  
  • CCR5 (predominantly)
  • CXCR-4

Question 3

Maraviroc

Answer 3

• Inhibits HIV entry
  
  • Binds CCR5 and prevents its interaction with the gp120 subunit of HIV Env (the viruses cell entry machienary)
  • Not effective for CXCR4-tropic HIV

Question 4

HIV Entry/Fusion Inhibitor

Answer 4

• Target the HIV envelope protein (gp120/gp41)
• Prevent env, specifically gp41 subunit from carrying out fusion of the virus and host membrane

Question 5

Enfuvirtide

Answer 5

• Fuzeon ®
• Roche ®
• Entry/Fusion inhibitor
• Binds to transient prehairpin intermediate coformation of gp41 during fusion

Question 6

Nucleoside RT Inhibitors

Answer 6

• Target drug to dNTP active site, just as with nucleoside inhibitor such as acyclovir and herpesvirus DNA polymerase

Question 7

Non-Nucleoside RT Inhibitor

Answer 7

• bind to an allosteric site of RT and decrease RT activity

Question 8

HIV Reverse Transcriptase

Answer 8

• Transcribes RNA genome into DNA so that it can be incorporated into the host genome and passed onto all progeny cells
• Analgous to DNA polymerase, however, RNA template instead of DNA template
• Mutations are introduced at the RNA–>DNA step

Question 9

Raltegravir

Answer 9

• Inhibit HIV DNA viral integration
• Isentress ®
• Targets HIV integrase enzyme
  
  • drops viral loads by 2x vs standard (2NRTI) alone

Question 10

Protease Inhibitors

Answer 10

• HIV protease is homodimeric aspartyl protease
• Cleaves gag and pol polyproteins into functional subunits to produce mature HIV particles
  
  • gag: into capsid, matric, nucleocapsid
  • pol: into protease, reversetranscriptase, integrase

Question 11

Examples of Herpes Virus dsDNA

Answer 11

• (+)RNA made from dsDNA by host polymerase
• Virally genomic DNA by viral DNA polymerase
  
  • Can target specically with antiviral drugs that have specificity for viral polymerase over host polymerase
  • Not the case for pappilomavirus or polyomaviruses