5 - Nucleoside Analogues as Antiviral Agents Flashcards
What are nucleosides composed of?
A heterocyclic base and a sugar
The base can be either a purine or a pyrimidine, and the sugar can be ribose (RNA) or deoxyribose (DNA).
What results from the phosphorylation of a nucleoside?
Nucleotides
What is the function of the capsid in viruses?
Protective protein coat surrounding infectious nucleic acids
What is a virion?
The complete structure of a virus, including the nucleocapsid and any additional membraneous layers
What are the stages in the life cycle of viruses?
- Adsorption
- Penetrating and uncoating
- Replication and transcription
- Synthesis and assembly
- Virion release
What is the difference between (+) and (-) strand RNA viruses?
The (+) strand has a base sequence identical to mRNA, while the (-) strand has a complementary sequence
What is the role of thymidine kinase in the action of Acyclovir?
Essential for the first step in converting the prodrug to the active drug
True or False: AZT is selective in its action against HIV.
False
What is the kinase by-pass mechanism and a potential drawback?
A method that allows inactive phosphate derivatives of nucleoside analogues to penetrate the cell membrane and liberate bio-active nucleotides
What is the significance of the glycosidic bond in nucleosides?
Sensitive to acid-catalyzed hydrolysis
What are the two types of nucleic acids that viruses can contain?
- RNA
- DNA
What is Acyclovir used to treat?
Herpes infections
What is the mechanism of action of AZT triphosphate?
Inhibits reverse transcriptase and acts as a chain terminator of DNA synthesis
Fill in the blank: The important stages in the life cycle of viruses include adsorption, penetrating and uncoating, replication and transcription, synthesis and assembly, and _______.
Virion release
What is the primary challenge in developing antiviral drugs?
Viruses use most of the same enzymes as the host cell
What is a classic example of a nucleoside analogue?
AZT (3’-Azidothymidine)
What is the MOA of Acyclovir?
Describe the process of DNA chain termination by Acyclovir Triphosphate
What is a drawback of AZT?
Explain how kinetic bypass is applied to Tenofovir disoproxil and its mechanism of release.
In the synthesis of AZT, indicate the first step (Hint - 5’-OH group)
In the synthesis of AZT, indicate the second step (Hint - azide formation)
Indicate the mechanism for the synthesis of Acyclovir from 1,3-dioxolane
How would you make a nucleoside derivative more stable to the hydrolysis of its glycosidic bond?
