Anti-Virals and HIV medication Flashcards
What are the main limitations in the effectivenes of antivirals?
- Host immune response (is still needed to clear infection)
- resistance
- adherence to treatment
How do infections with RNA vs DNA viruses generally differ clinically?
- RNA viruses usually cause acute infections then get cleared (exept for retroviruses – >integration into host genome)
- DNA viruses are generally more likely to cause chronic infection (more complex genome)
What is the general structure of a Virus?
All viruses have:
- Genetic Material (RNA or DNA)
- encapuled by Capsid
- (protein shell surrounding the genetic material of the virus
- * Some have additional
- Lipid Envelope and
- Envelope Proteins
What kind of Virus is Hep B?
Which drug is used to treat it?
It is a (not fully) DS DNA virus
Treated with
- Nucleotide analogue: Tenofovir
- only can limit replication and progression not cure –> chronic management
What kind of Drug is Tenofovir?
What is it used to treat?
It is a Nucleotide analogue + Nucleotide Reverse Transcriptase inhibitors
Used for treatment of Hep B and HIV
What kid of Drug is Ribavirin?
What is it used for?
It is a nucleoside analogue (prevents viral RNA synthesis)
- used to manage Chronic Hep C infections
- but not anymore because other effective treatment is out (Boceprevir)
What is Broceprevir?
What is it used for?
It is a protease inhibitor
- can cure Hep C infections (but very expensive)
Which drugs can you use in the treatment of Hepatitis C?
What is their MOA?
- Ribavarin= nucleoside analogue for chronic managment of disease
- Boceprevir= protease inhibitor for cure of Hep C
What kind of Virus is Hepatitis C?
It is a SS RNA virus
What are the different stages in the HIV replication cycle?
What drug classes can be used in each of the steps?
- Attachment/entry
–> Attachment inhibitiors
–> Fusion inhibitors - Reverse transcription & DNA synthesis
–> Reverse transcriptase inhibitors
–> NRTI, NNRTI, NtRTI - Integration to host DNA
–> Integrase inhibitors - Viral transcription
- Viral protein synthesis
- Assembly & Budding
–> Protease Inhibitors
Explain the process of HIV attachement and Entry to the host cell
- Viral membrane proteins (HIV Glycoprotein (GP) 120) interact with Leukocyte membrane receptors (CD4) leading to
- Virus also needs to bind to co-receptor, either
- CCR5 or
- CXCR4
- GP 41 penetrates host cell and
- Viral capsid is endocytosed
Explain how drugs used in HIV treatment can stop Vius Entering the Cell
2 main entry-inhibitors:
- Enfuvirtide
- Binds to HIV GP41 transmembrane glycoprotein
- Prevents endocytosis of Capsid
- Maraviroc
- Blocks CCR5 chemokine receptor
- also prevents co-stimmulation and endocytosis
What is Enfuvirtide?
A drug used in HIV treatment to prevent entry into cell (Fusion inhibitor)
- binds to HIV GP41 transmembrane glycoprotein
Explain the use and MOA of Maraviroc
It is a anti-HIV drug used for preventing entering of HIV into cell
- blocks CCR5 chemokine receptor
Explain the replication of HIV Genome in the cell
Viral single-stranded RNA is turned into double stranded DNA by reverse transcriptase
Which drugs and drug classes are available for inhibition of HIV replication inside the cell?
All inhibit Reverse transcriptase (inhibition of DS DNA synthesis (form SS RNA))
- Nucleoside RT inhibitors (Prodrug)
- Activated by 3 step phosphorylation process
- E.g. Zidovudine
- Nucleotide RT inhibitors (Prodrug)
- Fewer phosphorylation steps required
- E.g. Tenofovir
- Non-nucleoside RT inhibitors
- No phosphorylation required
- Not incorporated into viral DNA
- E.g. Efavirenz
What kind of drug is Efavirenz?
When is it used?
Non-nucleoside RT inhibitors –> inhibits viral DNA synthesis (DS DNA from SS RNA)
Used in treatment of HIV
- No phosphorylation required
- Not incorporated into viral DNA
What kind of drug is Zidovudine?
When is it used?
Prodrug used in treatment of HIV
- needs 3 phosphorylations for activation
- is a nucleoside Reverse Trancriptase analogue and prevents DNA synthesis
Explain the process of integration of HIV DNA into host DNA
•Viral integrase inserts viral DNA into host DNA
Which drug targets HIV DNA integration into host DNA?
•Raltegravir = integrase inhibitors (stop incooperation of viral DNA into host DNA)
What is the MOA of Raltegravir?
When is it used?
It in an integrase inhibitor stoping
- incooperation of viral HIV DNA into host DNA
Explain the process of Assembly of an HIV after integration of viral DNA into host genome
- Gag precursor –> encodes all viral structural proteins
- Abtivated by: HIV protease cleaves Gag precursor protein
Explain how drugs can interfere with HIV assembly and release and name exmaples
Drugs can inhibit protease that cleaves GAG precursor, imporant for assembly of Virus
- Saquinavir= protease inhibior
- (might be boosted with Ritonavir)
Explain the MOA and Use of Saquinavir
Protease inhibitor used in HIV treatment (inhibits assembls of Virus)
