Antivirals Flashcards
What is the genetic material of a virus like?
It can be either RNA or DNA and it is in a capsid surrounding the genetic material
What do some viruses have around the outside?
Lipid envelope that is decorated by envelope proteins
What do both Hep B and Hep C have a tropism for?
Liver hepatocytes
How curable are Hep B and C?
Hep B isn’t curable and Hep C is
How do you treat Hep B?
All you can do is contain the viral replication and transform it into a chronic disease which is much less likely to cause cirrhosis, liver failure and liver cancer
How do you know if either Hep B or Hep C needs treatment?
A lot of people can clear them before they get a chronic infection. So if someone gets infected, you leave it 6 months to se if they clear it but if not it requires treatment
How is HepB treated?
Tenofovir- A nucleotide analogue- nucleotide reverse transcriptase inhibitor. It competes with endogenous deoxynucleotides that would be used to make up DNA- blocking DNA synthesis
How is HepC treated?
Ribavirin (nucleoside analogue) and peg interferon alpha. Ribivarin competes with endogenous nucleotides and prevents synthesis of RNA
Boceprivir- protease inhibitor
Effective against Hep C genotype 1 (most common)
What is the attachment and entry of HIV like?
Viral membrane proteins interact with leukocyte membrane receptors. This leads to viral capsid endocytosis
What is the replication and integration of HIV like?
Within the cytoplasm there is reverse transcriptase which converts viral RNA -> DNA. The DNA is then transported into the nucleus and integrated into host DNA
What is the assembly and release of HIV like?
Host cell machinery is used to produce copies of viral RNA and essential proteins. These are assembled to form new virus particles and mature virions are released
Describe the HIV attachment and entry process?
HIV glycoprotein 120 attaches to CD4 receptor on the T lymphocytes
GP120 also binds to either CCR5 or CXCR4
GP41 then penetrates the host cell membrane and the viral capsid enters
What does enfuvirtide do?
It binds to GP41 on HIV and blocks fusion of the virus with the host cell membrane
What does maraviroc do?
Blocks the CCR5 chemokine receptor
What are long term non-progressors in terms of HIV?
These are people with a polymorphism in CCR5 receptor so HIV can infect them but can’t enter their cells
What is reverse transcription?
When viral RNA is converted to double stranded DNA by reverse transcriptase
What are used to inhibit HIV replication (reverse transcription)?
Nucleoside reverse transcriptase inhibitors -activated by 3 step phosphorylation process e.g. Zidovudine
Nucleotide reverse transcriptase inhibitors- fewer phosphorylation steps required e.g. Tenofovir
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
How do nucleotide/nucleoside reverse transcriptase inhibitors work?
They compete with endogenous deoxynucleotides/deoxynucleosides thus inhibiting the action of reverse transcriptase
How do non-nucleoside reverse transcriptase inhibitors work?
No phosphorylation is required, they aren’t incorporated into DNA. They bind to reverse transcriptase and cause a change in the shape of the enzyme -> blocks HIV replication e.g. Efavirenz
What does viral integrase do?
It inserts the viral DNA into the host DNA
Name an integrase inhibitor?
Raltegravir
What does a virus need after it has replicated and produced a capsid?
It needs some other components to be synthesised to make it a complete virus that can go and infect other cells
What is Gag?
It is a gene that encodes all viral structural proteins
What does HIV protease do?
It cleaves Gag precursor protein releasing the proteins that go on to make up the complete virus
What is saquinavir?
First generation protease inhibitor which has a low bioavailability so isn’t a very good drug
What does low dose ritonavir do?
Reduces the metabolism of the protease inhibitor which allows saquinavir to reach therapeutic concentrations- they are commonly used together
What type of virus is herpes simplex virus?
dsDNA virus
What is HSV dsDNA surrounded by?
Tegument and enclosed in a lipid bilayer
What is the tropism for HSV1 and HSV2?
HSV1- Cold sores
HSV2- Genital herpes
How is herpes treated?
Acyclovir- nucleoside analogue
Why is acyclovir very specific?
One of the phosphorylation steps requires viral kinases
What type of virus is influenza?
Multipartite single stranded RNA virus
What is important for the release of influenza into the host cell?
Envelope protein neuraminidase
What is the tropism for influenza?
Nose, throat and bronchi
What is oseltamivir?
Neuraminidase inhibitor
