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
- Penetration 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
Who developed the first vaccination, and what disease did it target?
Edward Jenner; smallpox
What is a classic example of a nucleoside analogue?
AZT (3’-Azidothymidine)
What is the role of viral enzymes in some nucleocapsids?
Essential for replication
What happens to the nucleic acid during the penetrating and uncoating stage?
It is introduced into the host cell
What type of nucleic acid do most RNA viruses contain?
Single-stranded RNA (ssRNA)
What is the main reason for the toxicity of AZT?
It inhibits human DNA polymerase and is generated in all cells
What is the main advantage of Acyclovir compared to AZT?
Acyclovir is very selective in its action and is not toxic to the patient
What stabilizes the glycosidic bond in nucleosides?
Fluoride substitution
List examples of nucleoside analogues used as antiviral drugs.
- Acyclovir
- AZT
- Tenofovir
- Saquinavir
- Nelfinavir
- Amprenavir
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?
