Antivirals Flashcards
Structure of virus
Genetic materia (RNA or DNA)
Surrounded by capsid (protein shell surrounding the genetic material of the virus)
SOME HAVE:
Then lipid envelope + envelope proteins
Tropism of hepatits
Liver hepatocytes
T/f there is a cure for hep B and hep c
F….. there is no cure for hep B… it is chronic infection
there is now a cure for hep C (=ribavarin))
What type of genetic information in hep B
DNA
Which drug used to treat hep B
Initial treatment is pegylated interferon alpha 2a
then
Tenofovir/lamivudine = nucleotide analogue,
(also a reverse transcriptase inhibitors )
What type of virus is hep C
RNA
What was hep C treated with
Interferon
Wht is the current hep C treatment
Ribavirin & Peginterferon alfa
Ribavirin = nucleoside analogue prevents viral RNA synthesis
Boceprevir = protease inhibitor
-Most effective against Hep C genotype 1
HIV: Attachment and entry phase
- Viral membrane proteins interact with leukocyte membrane receptors
- Viral capsid endocytosis
HIV: Replication and integration
Within cytoplasm - reverse transciptase enzyme converts viral RNA to DNA
DNA transported into nucleus & integrated into host DNA via integrase
HIV: assembly and release
Host cell’s ‘machinery’ utilised to produce viral RNA & essential proteins
Virus is assembled within cell –> mature virion is released
Receptors involved in attachment and entry of HIV
HIV Glycoprotein (GP)120 attaches to CD4 receptor
GP120 also binds to either CCR5 or CXCR4
GP41 penetrates host cell membrane & viral capsid enters
Drugs affecting HIV entry into host cell
Enfuvirtide
-Binds to HIV GP41 transmembrane glycoprotein
Maraviroc
-Blocks CCR5 chemokine receptor
What drugs affect HIV replication
Nucleoside RT inhibitors
Activated by 3 step phosphorylation process
E.g. Zidovudine
Nucleotide RT inhibitors
Fewer phosphorylation steps required
(also used for Hep B)
E.g. Tenofovir
Non-nucleoside RT inhibitors
No phosphorylation required
Not incorporated into viral DNA
E.g. Efavirenz
Outline drugs interfering with HIV integration
Integrase inhibitors
Raltegravir - first of 3 licensed integrase inhibitors
What is the use of HIV protease i assembly and release
Gag precursor –> encodes all viral structural proteins
HIV protease cleaves Gag precursor protein
Which drugs are protease inhibitors
Saquinavir - 1st generation PI
Low dose Ritonavir reduces PI metabolism –> co-administered as ‘booster’
Boceprivir is a PI used to treat hep C
What type of genetic material does HSV have
and what is the structure
Double-stranded DNA
Surrounded by tegument & enclosed in a lipid bilayer
State the different types of HSV
Herpes Simplex Virus (HSV)-1 –> cold-sores
HSV-2 –> genital herpes
Which drug is used for HSV?
Nucleoside analogues –> Aciclovir
A guanine analogue
Used in CMV and EBV too
What type of genetc material on influenza
Multipartite single stranded RNA virus
What are the two envelope proteins on HIV
Neuroaminidase/haemagglutinin
What is neuramindase important for
Release of the virus
Tropism of influenza
Multipartite single stranded RNA virus
What is the treatment for influenza
Neuraminidase inhibitor –> Oseltamivir or zanamivir
Virus cannot be released from the cell
T/F olsetamivir is very efficacious
F… doesn’t reduce rate of hospitilisation
(probably because there is a few days of incubation in which influenza is replicating in cells but you’re aymptomatic at this point. By the time you realise you have flu then take it, too many cells have already been infected. Better to take flu vaccine)
Why are viruses unable to reproduce on their own
Since they do not have a defined cellular structure or their own metabolism
So referred to as obligate parasites
What does the viral genetic material contain information for
contains:
1. The information that is required to create its own microenvironment
2. Program the synthetic machinery of th`e host cell for viral replication.
What is the function of the viral capsid
- protect the genetic material from dangers such as nucleases in the external environment.
- an also play an important role in attachment of the virion to the host membrane, which would ordinarily repel the negatively charged DNA or RNA.
What is the nucleocapsid
he capsid and the viral genome along with any associated nucleoproteins are referred to as the nucleocapsid.
Where is the lipid envelope (derived from
A number of viruses also have a protein coat, which is a lipid bilayer quite often derived from the membrane of the host cell
Integral membrane proteins and glycoproteins coded for by the viral genome.
These integral membrane proteins often play an important role in the entry and exit of viruses into host cells.
6 stages of typical life cycle of virus
- Viral attachment
- Entry
- Uncoating
- Replication
- Assembly
- Release
Outline the three methods of viral entry into cells
Clathrin-mediated endocytosis.
Caveolar endocytosis
Plasma membrane fusion
Why is uncoating important and what is carried out by
This refers to removal of the PROTEIN CAPSID.
This occurs so that the genetic material can come into direct contact with the cellular machinery that it will utilise for replication
degradation of the capsid involves a variety of different proteins and enzymes, which are produced by both the host cell and the virus.
Outline the type of replication that occurs for each of the following types of virus:
- +ve ssRNA
- -ve ssRNA
- Dipliod +ve ssRNA retrovirus
- Double stratnded RNA
- DNA virus
- +ve ssRNA: These can produce proteins (i.e. induce translation) directly by utilising the hosts’ ribosomes
- -ve ssRNA: hese cannot produce protein directly and must contain the appropriate transcriptase allowing the host ribosome to create the complementary +ve RNA strand.
- Dipliod +ve ssRNA retrovirus: These contain a reverse transcriptase enzyme allowing the host cell to produce DNA from the viral genome
- Double stranded RNA: contain all the necessary templates to produce the proteins and RNA templates required for replication.
- DNA virus: These viruses generally have the means for transportation into the host nucleus.
Differentiate +ve and -ve ssRNA in terms of replication
+ve ssRNA can induce translation directly (i.e. can act as mRNA molecule)
-ve ssRNA cannot produce protein directly (must contain a transcriptase to convert it into +ve ssRNA for reading by ribosome
Outline how assembly can differ between viruses
Differs depending on whether the virus has lipid envelope
NON-EVELOPED: Just requires construction of capsid
ENVELOPED: closely associated with the release stage and involves the formation of ‘docking stations’ within the host membrane by viral proteins. Once the viral proteins have replaced the host proteins in the membrane the nucleocapsid attaches itself (i.e. docks) to the inner surface of the membrane
Outline the release phase of virus lifecycle and the differently types
- Disintegration of host cell
- Budding (host cell in tact)
For enveloped viruses once the nucleocapsid is attached to the ‘docking station’ it becomes wrapped up within the patch of membrane and ‘buds’ off into the extracellular environment.
Structure of HIV including genetic material
Large
2 copies of ssRNA in icosahedral capsid.
This in turn is surrounded by a phospholipid envelope containing numerous transmembrane glycoprotein complexes
Which cells can HIV infect
HIV has the ability to infect a variety of immune cells including CD4+ T-lymphocytes, monocytes and macrophages.
First ARV?
Zidovudine
How are the following named hepatitis viruses spread
HAV/HEV fection result in very similar symptoms and can be controlled by good hygiene and sanitation
HBV spready by exposure to infected blood or bodily fluid
HCV spread through blood contact (mainly infected needles or blood transfusions)
What is a subviral satellite
it requires another virus (in this case HBV) to assemble and infect new cells.
=HDV
What is the consequence of chronic HBV infectin
Although around 95% of adults spontaneously recover from the illness, chronic infection
can lead to life threatening complications such as cirrhosis.
What is the consequence of long term hep c infection
The majority of individuals who are acutely infected become chronically infected, which can lead to advanced liver disease and hepatocellular carcinoma.
(differs to HBV, where 95% spontaneously recover)
What type of virus is varicella zoster and what can it cause in childhood and adultood
Herpes
Varicella zoster is responsible for causing chicken pox upon primary infection. Chicken pox is a highly contagious acute illness generally affecting young children, resulting in itchy lesions (pox)
on the skin.
Once the illness has resolved the virus is not eliminated and lies latently within the nerve cell bodies. The virus can subsequently become reactivated many years later causing shingles.
What is treatment for varicella zoster
The antiviral compounds recommended for the treatment of HSV and varicella zoster include the nucleoside analogue aciclovir.
Same as other herpes
How many segments of the influenza genetic material
multipartite genome of linear single-stranded RNA divided into 7-8 segments
How is influenza transmitted
highly contagious and is transmitted through the air or via numerous bodily secretion
Clinical manifestation of influenza
fever, cough, myalgia and general malaise.
