Antiviral Drugs Flashcards
How are viruses classified?
- Type and structure of nucleic acid and the strategy of its replication.
- Symmetry of capsid.
- Presence or absence of lipid membrane
What are the stages un viral life cycle?
1) Attachment
2) Penetration
3) Disassembly (release of viral genome),
4) Transcription
5) Translation
6) Replication
7) Assembly
8) Release
Name and describe the three mechanisms of antivirals
Virucides - These directly inactivate viruses eg, detergents, UV light, cryotherapy.
Antivirals - Inhibit replication at cellular level but therefore aren’t effective in elimination of nonreplicating viruses.
Immunomodulators - Replace deficient host response or enhance endogenous response
Describe some of the targets for antiviral drugs
- Entry inhibition,
- Viral disassembly,
- Viral replication (Viral polymerases, viral proteases, integrase),
- Viral release inhibitors
What is the function of nucleotide analogues?
The competitively inhibit the action of viral polymerase which inhibits new viral DNA production
Describe features of retroviruses
- Positive sense single stranded RNA virus.
- Need for reverse transcriptase to make DNA copy of viral RNA. The DNA copy is then integrated into the genome of host cell and terminated as provirus. The provirus DNA is then transcribed into new genomic RNA and mRNA for translation into viral proteins.
Describe the process of HIV entry
It is mediated by envelope glycoprotein spike (mainly gp120) which binds to a CD4 receptor and one of the two co-receptors CCR5 or CXCR4
What is the significance of CCR5 co-receptor
A mutation in this receptor has resulted in HIV being unable to bind to cells. Therefore this is a good target for treatment.
Give examples of entry inhibitors
- Fusion inhibitors eg, Enfurvitide (T20) (not used often as it is toxic) prevents the viral cells from fusing with host cell and releasing viral genome.
- CCR5 antagonists, eg, Maraviroc
What are the two reverse transcriptase inhibitors?
- Reverse transcriptase inhibitor .
- Non-Nucleoside reverse transcriptase inhibitors
Name some drugs in the nucleotide reverse transcriptase inhibitors (NRTIs) and their side effects
Abacavir (analogue of guanosine) - SE = ischaemic heart disease
Tenofovir (Analogue of adenosine) - SE = Decreased bone mass density, osteomalacia, increased fracture risk
(Emtricitabine and lamivudine)
NRTIs are prodrugs, what is needed to activate them?
Phosphorylation by viral and/or cellular kinase.
Name two examples of NNRTIs
Efavirenz
Rilpivirine
Both drugs can cause neurological and psychiatric AE.
Describe the mechanism of HIV protease inhibitors
Virus specific protease gives rise to various functional proteins and since the protease doesn’t exist in host it is selective.
Name some examples of protease inhibitors and their side effects
Darunavir (ischaemic heart disease and nephrolithiasis) , Atazanavir (nephrolithiasis)