Antiviral Agents and Resistance Flashcards
Why are all antivirals virustatic?
Because the drugs cannot kill the viruses rather can only inhibit their growth until the immune system is able to kill it itself
What are challenges when creating a effective antiviral agent?
Often toxic to human cells
Accumulation of side effects with long term use
Pharmacokinetic changes over time
Selection of viral resistance
What are the potential sites of activation for antiviral agents?
- ) Attachment: block viral ligands or cell receptors with antibodies or chemicals
- ) Proteins: involved in penetration and uncoating
- ) Viral and host proteins involved in DNA/RNA synthesis
- ) Viral gene expression: antisense oligonucleotides, interferons and siRNA to
- ) Viral assembly
- ) Viral proteins involved in release
How can interferons be used against viruses?
IFN induces synthesis of either 2’,5’-oligoadenylate synthetase or protein kinase: 2’,5’ degrades viral mRNA and protein kinase produces eIF-2 which inhibits protein synthesis
What is pegylation and what does it do?
Interferons combined with polyethylene glycol to enable slow release of interferons to decrease negative side effects
How do Nucleoside/Nucleotides Reverse Transcriptase Inhibitors (NRTI) work?
Stop DNA replication by inhibiting DNA polymerase
What are the two most important NRTIs against HIV?
AZT and Zidovudine
How do AZT and Zidovudine work?
Competitively inhibit DNA polymerase by being incorporated into DNA chain; they mimic deoxythymidine and prevent extension due to lack of 3’-OH
What is a better drug Nucleosides or Nucleotides?
Nucleosides because they are more penetrating than nucleotides (negative group blocked by membrane)
What is a nucleoside?
Nucleotide minus the phosphate group
How is Zidovudine activated?
By Reverse Transcriptase turning Zidovudine to ZTP
What are Non-nucleoside RT Inhibitors (NNRTI)?
Allosteric inhibitors of RT
Why are NNRTI not always effective?
RT is an enzyme so it easily mutates
What are common NNRTI?
Nevirapine and Efavirenz
How do protease inhibitors work against HIV?
HIV produces polyproteins that are cleaved by a protease, these proteases can be substituted by a peptide that decoy as the protease and competitively inhibit the proteases
