T1: Acyclovir, An Antiviral Agent Flashcards
Q: What is a nucleoside?
A: base and sugar
Q: What is the structure of double stranded DNA?
A: one goes from 5’ to 3’ and other in other direction
bases are joined by hydrogen bonds
5’ end is phosphate
5’ end is hydroxyl group
antiparallel strands
Q: How does replication of double stranded DNA take place?
A: DNA is unwound using helicase and topoisomerase
DNA polymerase synthesises dsDNA
semi conservative replication
Q: What is the structure of acyclovir and how does it compare with nucleosides found in double stranded DNA?
A: It has no –OH group which means it is unable to form glycosidic links to other nucleotides, causing chain termination
double ringed structure
Q: What is the active compound in acyclovir, what enzymes are required?
A: active compound = acyclo-GTP
acyclovir is not biologically active until activated by thymidine kinase- acyclovir is phosphorylated -> acyclo-guanasine-mono-phosphate (acyclo-GMP) plus guanylate kinase -> acyclo-GDP plus phosphotransferase -> acyclo-GTP
Q: What is the mode of action of acyclovir?
A: Acyclovir works by chain termination during the DNA replication stage of the herpes virus. It prevents it from replicating so than mRNA copies of the DNA cannot be generated to produce proteins and further its life cycle.
It is favourably incorporated by viral DNA polymerase instead of deoxyguanasine
Q: What is the mechanism of resistance of acyclovir?
A: Resistance to acyclovir is brought about through mutations in the genetic information coding for the active site which occur very frequently in viruses primarily due to the generation time and number of bp.
Q: What is the spectrum of activity of acyclovir?
A: It targets herpes simplex virus HSV and some of the other forms of Herpes
virus just needs to be large enough to have own DNA polymerase and thymidine kinase
Q: What are viruses? What form is their genetic material in? Organelles? Classed as cells? Do they reproduce within or outside of cells?
A: obligate parasites, with genetic material in the form of DNA/RNA. They have no organelles and are not cells – they cannot reproduce outside of cells
Q: How do small and large virii vary? Bigger means?
A: There are small and large virii, relating to amount of genetic material they have, and so the amount of virus specific genes.
Thus, the bigger the virus, the more proteins that differ from the host and the more potential targets for drug intervention and hence therapy against that virus
Q: What is the basic strategy taken for drugs?
A: The basic strategy is the relation of protein structure to function – we take advantage of the difference between viral and human protein isoforms and utilise them to perturb key viral life cycle processes without affecting the patient
Q: Using the example of an archetypal large DNA virus (herpes virus) describe the major features of the life-cycle.
A: virus on outside of host cell with its own DNA and a coat protein
enters
coat protein is broken down
DNA is replicated via semiconservative replication while DNA is also transcribed -> mRNA and translated to get more coat protein
assembly
exit
