Mechanism of Action of Anti Viral Drugs Flashcards
What is the basic structure of a virus?
small infective agents consisting of RNA or DNA enclosed in a protein coat
how do viruses replicate?
they have no metabolic machinery and therefore use the host cell metabolic processes which they infect
What do viruses use to attach to a host cell? What do they attach onto?
- polypeptides on the envelope or capsid
- bind onto normal membrane receptors for things like cytokines, neurotransmitters ore hormones
what process do viruses use to enter the host cell once bound to the surface?
receptor mediated endocytosis
What is the main target for entry inhibitors?
viral fusion with the host cell
what are the 2 main entry inhibitors used?
entry inhibitor- Maraviroc
fusion inhibitor- Enfuviritide
which viruses are entry inhibitors used against?
-retroviruses- HIV as an example
How does HIV enter a host cell? What mediates its entry? What is the receptor? What are the co-receptors?
mediated by Env glycoprotein spike trimer of gp120 and gp41
receptor CD4 is required and a co-receptor CCR5 or CXCR4
What is the mechanism of action of the entry inhibitor Maraviroc?
binds to co-receptor CCR5 preventing its interaction with gp120
What is the mechanism of action of the fusion inhibitor Enfuviritide?
binds to gp41 and interferes with its ability to approximate the 2 membranes
What are examples of drugs which prevent viral uncoating?
Amantadine and rimantadine
What is the mechanism of action of the viral uncoating drugs?
block the M2 ion channel involved in virion uncoating following endocytosis
What is the mechanism of nucleoside analogue chain terminators?
compete with natural substrate in DNA or RNA polymerisation.
Chain termination comes from not offering 3’-hydroxyl function at the 2’-deoxy ribose moiety required for the attachment of incoming nucleotide
What type of drug are nucleoside analogues? what is their active form?
- prodrugs- requiring intracellular phosphorylation by viral and or cellular kinases converting them to
- 5’-triphosphates
What is an example of a nucleoside analogue?
Aciclovir
What sort of viruses are nucleoside analogues used to treat?
DNA viruses
What is Aciclovir used against?
- herpes simplex virus: genital herpes simplex, herpes simplex labialis
- varicella zoster virus: chicken pox, shingles
- prevention of herpes viruses in immunocompromised patients
How do nucleoside reverse transcriptase inhibitors work?
binds to the chain of DNA to being transcribed terminating it early rendering it useless since its incomplete
now do no nucleotide reverse transcriptase inhibitors function?
bind to the reverse transcriptase enzyme itself and denature it so it can’t produce viral DNA
What are examples of nucleoside RT inhibitors?
-lamivudine, abacavir, zidovudine stavudine
what are examples of non nucleoside RT inhibitors?
delaviridine, efavirenz, etravirine, nevirapine
What is the mechanism of action of protease inhibitors?
host mRNAs code directly for functional proteins.
virus specific protease then converts them into various functional proteins
protease does not occur in the host making it a target
What are examples of protease inhibitors?
atazanvir, indinavir, lopinavir, ritonavir, saquinavir
What are protease inhibitor used to treat?
hepatitis C virus
Which protease inhibitors are used against hepatitis C?
Telaprevir and Boceprevir
What is the function of HIV integrase?
mediates2 reactions: 3’ end processing of double stranded viral DNA ends.
strand transfer which joins viral DNA to host chromosomal DNA
What are 3 examples of integrase inhibitors?
- Raltegravir
- Elvitegravir
- Dolutegravir
What is the function of virus release inhibitors?
stops transmission within host by stopping transmission of virus from cell to cell
what is an example of virus release inhibitors?
influenza Neuraminidase inhibitors
what is the function of Neuraminidase during influenza infection?
NA- functions in influenza infection by cleaving sialic acid from cell surface so that newly made viruses are released and able to spread to uninfected cells
how do NA inhibitors function?
replicate structure of sialic acid and bind to the active site on NA hence preventing its function
what are 2 NA inhibitors?
Zanamivir
Oseltamivir
What is an example of an immunomodulator and what is it used to treat?
- Peg interferon alpha
- Hepatitis C and B virus
