1. Antivirals Flashcards
What is an antiviral?
A drug that is effective against viruses by killing them/suppressing their ability to replicate.
How many people were living with AIDS worldwide in 2012? How many were newly infected?
- 3 million
- 2.3 million newly infected
What happens to CD4+ T cells after infection with HIV?
Initially decrease (~6 weeks)
- then increase
- then gradually decrease over years»_space; death
What happens to the number of copies of HIV RNA once infected?
Initially increase rapidly (~6 weeks)
- then decrease
- years later increase again»_space; death
What type of molecule tends to cause acute viral infections?
RNA
-don’t survive well
Give some examples of acute viral infections.
Influenza, measles, mumps, hep A
What type of molecule tends to cause chronic viral infections?
DNA
-relatively stable
How is HIV different from most chronic viral infections?
Caused by single-stranded RNA, but is copied to DNA during replication
What are the 2 types of chronic infection?
Latent (lying dormant)
Persistent (continuing to exist)
Give some examples of latent chronic viral infections.
Herpes simplex, cytomegalovirus
Give some examples of persistent chronic viral infections.
HIV, hep B, hep C
What do viruses consist of?
Nucleic acid (DNA/RNA)
Protein (coat/enzymes)
+/- Lipid envelope
What sort of parasite are viruses?
Intracellular
-they only replicate in cells
What are the 2 types of proteins that most viruses are composed of?
STRUCTURAL (core proteins - GAG, envelope proteins - ENV)
NON-STRUCTURAL (enzymes -POL)
What are the stages of viral replication? (8)
- Virus attaches to cell (receptor)
- Cell entry
- Virus uncoating
- Early protein production (viral enzymes)
- Replication
- Late transcription/translation (viral structural proteins)
- Virus assembly
- Virus release
Do most viruses kill the cells they infect?
No, they get released and»_space; infect other cells
How do we use the proteins that viruses encode to treat viral infections?
They are unique proteins, so they are targets for molecular inhibition (anti-viral activity)
What are the reactions that polmerases catalyse? (4)
- DNA to DNA
- DNA to RNA
- RNA to RNA
- RNA to DNA
Where are DNA to DNA/RNA polmerases found?
Eukaryotes
DNA viruses
Where are RNA to RNA polmerases found?
RNA viruses
-not eukaryotes
Where are RNA to DNA polymerases found?
Retroviruses (HIV)
Hep B
(-not eukaryotes)
What type of drug is azidothymidine (AZT)?
Nucleoside Reverse Transcriptase Inhibitor (NRTI).
What was azidothymidine developed as, and what is it now used to treat?
- Developed as an anti-cancer drug, but too toxic against normal cells
- Now used to slow progressions of HIV as it works at lower concentrations (but it can become resistant)
What are NRTIs?
Nucleoside Reverse Transcriptase Inhibitors
- antiretroviral drugs used to treat HIV
What are the main types of NRTIs?
- PYRIMIDINE ANALOGUES (thymidine & cytosine)
- PURINE ANALOGUES (adenine & guanidine)
Give 2 examples of pyrimidine analogues.
THYMIDINE: Zidovudine
CYTOSINE: Lamivudine
Give 2 examples of purine analogues.
Abacavir
Tenofovir
Which NRTIs are also effective against Hepatitis B, and why?
Lamividine & tenofovir
-Hep B contains reverse transcriptase enzyme
What are NNRTIs and how do the work?
Non-Nucleoside Reverse Transcriptase Inhibitors.
-also inhibit reverse transcriptase (HIV prevention)
Give 2 examples of NNRTIs.
Efavirenz
Nevirapine
What are protease inhibitors (PIs)?
A class of antiviral drug commonly used to treat HIV and hepatitis. -Inhibit unique proteases in viruses
Give some examples of protease inhibitors.
Atazanavir Darunavir Lopinavir Nelfinavir Ritonavir
-NB. -avir
What is special about Ritonavir as a protease inhibitor?
It inhibits liver enzymes that break down other antivirals, so is used to “boost” the levels of other PIs.
Name 3 newer HIV drugs.
- Fusion inhibitors
- Integrase inhibitors
- Chemokine receptor antagonists (co-receptor)
Give an example of a fusion inhibitor (HIV drug).
Enfuviritide
-T20, given by IM injection
Give an example of an integrase inhibitor (HIV drug).
Raltegravir
-prevent replication/fusion of the genome
Give an example of a chemokine receptor anatagonist (HIV drug).
Maraviroc (CCR-5)
-blocks entry to cells
What does HAART stand for?
Highly Active Anti-Retroviral Therapy
What does HAART consist of?
- 2 NRTIs & NNRTI
- 2 NRTIs & boosted PI
When is HAART used?
HIV treatment. Started when CD4+ decreases and taken lifelong
-aims to decrease viral load & prevent additional infection
How many nucleotides does the HIV genome contain?
~9000 nucleotides
-each contains 1+ mutations»_space; more adaptability to change
What HIV mutation results in resistance to Lamivudine?
M184V mutation
How could HIV potentially be cured?
Supressed on antivirals & destroy existing CD4 lymphocytes by conditioning
» stem cells restored by donor
What would be the criteria for an HIV stem cell donor?
- HLA-matched
- Delta 32 homozygous allogenic
What are interferons?
Proteins released by animal cells that inhibit viral replication (naturally occurring antivirals).
How is hepatitis C treated?
Interferons & ribavirin.
- must be given from 3-12 months & can»_space; depression
What are the 5 important antivirals?
Aciclovir Ganciclovir Oseltamivir & Zanamavir Ribavirin Interferons
What is Aciclovir used to treat?
Herpes Simples (Rx)
Varicella Zoster
(nucleoside analogue)
What is Ganciclovir used to treat?
Cytomegalovirus
What are Oseltamivir & Zanamavir used to treat?
Influenza
What is Ribavirin used to treat?
Hepatitis C
RSV
What are Interferons used to treat?
Hepatitis C
Hepatitis B
