Antivirals Flashcards
What is required by a good antiviral?
- High therapeutic index
- Easy to administer
- Easy to store
- Cheap to produce
- Broad scale use
What is a high therapeutic index?
This is an antiviral which has a high antiviral activity but low cellular toxicity
What is helping us to develop new anti-viral drugs?
Rational drug design
3D structures of molecules
Crystal structures
What are the nucleoside analogue chain terminators you must know?
- HSV: Ganciclovir and acyclovir
- HCV: Ribavarin
- HIV: AZT: Azidothymidine
What nucleoside analogues can be used to treat HSV infection?
Acyclovir and ganciclovir
Acyclovir is a?
Prodrug
Acyclovir action?
It is phosphorylated by the viral thymidine kinase to become acyclovirir-monophosphate
It is then phosphorylated into acycloviur-triphosphate by cellular kinases and can act as a chain terminator during DNA synthesis
How does acyclovir prevent cellular toxicity?
It has a higher affinity for viral polymerase than for host polymerase
What is the main difference between ganciclovir and acylclovir?
Ganciclovir has an additional hydroxymethyl group
Ganciclovir must be injected and cannot be applied topically like acyclovir
Why is acyclovir easier to administer?
Topical application is possible
What is the nucleoside analogue used to treat HCV hepatitis C infection?
Ribavirin which is a chain terminator
It is a guanosine analogue
What nucleoside analogue can be used for HIV treatment?
Azidothymidine = AZT
Azidothymidine is what class of drug?
NRTI
What is an NRTI?
Nucleoside reverse transcriptase inhibitor
How can resistance to AZT develop?
Via mutations in the gene encoding the reverse transcriptase
What therapy is used in HIV treatment?
HAART
What does HAART stand for?
Highly active anti retroviral therapy
What does HAART therapy involve?
It involves the use of multiple antivirals which when used in combination should reduce resistance developing
What is used in combination therapy for HIV?
Integrase inhibitors Protease inhibitors NRTI nucleoside RT inhibitors NNRTI non-nucleoside RT inhibitors Entry inhibitors Anti-fusion class of drugs
What is an example of a HIV entry inhibitor?
Maraviroc
What does Maraviroc do?
It binds to CCR5 and prevents HIV binding
What homozygous mutation makes individuals resistant to HIV?
CCR5-delta 32
The first man cured of HIV?
Timothy Brown- 2007
How was Timothy Brown cured of HIV?
He has leukaemia and was given a haematopoietic stem cell transplant from a donor who was homozygous for the CCR5 delta 32 mutation
Why are so many drugs against HIV required?
So they can be used in combination to reduce the likelihood that resistance will develop
What is the name of the HIV combination therapy?
HAART
HAART stands for?
Highly active anti retroviral therapy
The CCR5 delta 32 mutation is most common in?
Caucasians
Drugs against rhinovirus include?
Pocket factor lipid mimics
IMP-1088
Which drugs target the host?
Maraviroc targeting host CCR5
Imp-1088 targeting the host N-myrostoyltransferase
Which drug can mimic the pocket factor lipid?
Pleconaril
What is the host N-myristoyltransferase used for?
To N’ myristoylate the VP0. This allows assembly of the capsid
What drugs can be used against HCV?
- Ribaravin nucleoside chain terminator
- Drugs targeting NS5B polymerase
- Anti-protease drugs targeting NS3/4A
- NS5A inhibitors
NS5A is involved in?
Formation of the membranous web
Ribaravin is what?
A nucleoside chain terminator, guanosine analogue