Flashcards in antiviral drugs Deck (10):
targets of the antiviral agents:
Targets of the antiviral agents
1. DNA/RNA synthesis inhibition
A. Nucleoside / nucleotide analogs:
** Need activation (2 or 3 phosphorilations) –triphosphate derivatives blocks DNA / RNA polymerase and / or cause chain termination after incorporation
B. Non competitive inhibitors (NNRTI, foscarnet, HCV)
2. Entry inhibitors (maraviroc, enfuvirtid)
3. Uncoating inhibitor (amantadin),
Targets of the antiviral agents
1. Other viral enzyme inhibitors
Kinase inhibitor (CMV)
Terminase inhibitor (CMV)
Protease inhibitors (HIV, HCV)
Integrase inhibitors (HIV)
Neuraminidase inhibitor (Influenza)
2. Immunological agents
Agents against herpes viruses I.
Agents for HSV 1, 2 and VZV
Aciclovir and Valaciclovir:
Which analogues are they? who is a prodrug?
Aciclovir taken? 3
Valacyclovir taken? 1
-Guanosine analogs (nucleosides).
valacyclovir prodrug of aciclovir
- The ACV treatment not eradicates the latent viral colonization
They need triple phosphorylation, which the first step is done by the virus enzme of infected cells (thymidilate kinase)-> inhibits viral DNA polymerase.
An intermediate ACV-TP is also selective for viral DNA polymerase.
A. iv. B. po (low bioavailability- 15%) C. local),
B. Valaciclovir (po. high bioavailability).
It penetrates into secretes and into CNS well.
It is eliminated by the kidney (by filtration and secretion).
Adverse effects: well tolerated with oral form (might cause vomit and nausea).
If high Dose IV-> treatment hydration is important to prevent crystaluria).
Not teratogenic: it is given in case of active herpes to prevent vertical transmission.
Agents against herpes viruses III.
Agents for HSV 1, 2 and VZV:
Penciclovir is an ACV analogue but it not causes DNA chain termination.
admin: (local) for such as local herpes.
Adverse effects: headache, diarrhea, nausea
HSV and VZV
gangiclovir (guanosine analogue)
valganciclovir (another guanosine analogue)
mechanism: similar to acyclovir.
Mostly used in CMV prophylaxis of MV infection including retinits, in aids and transplant patients.
Given IV for ganciclovir.
Given oral for valganciclovir.
Hematotoxicity (leukopenia and thrombocytopenia),
mucositis, fever rash and crystalluria.
Can Cause seizures in high doses.
Cidofovir (cytosine analog)
a deoxy-cytosine mono phosphate.
mechanism: phosphorylation does not depend on the viral thymidine kinase.
excreted by tubular secretion.
Spectrum: Herpes viruses and other viruses such as
adeno, polio,pox and papilloma virus.
IT is a good antiviral drug against ACV and GCV resistant viruses.
Method of admin
A pyrophosphate (so not a metabolite) derivative which non-competitive inhibitts the RNA polymerase enzyme (blocks cleavage of diphosphates during incorporation into the DNA).
Penetrates to CNS.
secretion via kidneys
HSV (acyclovir resistant),
Also used in HIV with ganciclovir combo.
1) Nephrotoxic-> ATN +electrolyte imbalance.
2) bone alterations (due to bone accumulation of drug).
3) CNS effects.
1) monophosphorylated form inhibits IMP dehydrogenase.
2) Triphosphate inhibits VIRAL RNA polymerase and end capping of viral RNA.
Broad spectrum... (both RNA and DNA viruses)
HSV, VZV, influenza (a and B), RSV and more..
Mainly used in
adjunct to alpha interferons in hep C.
Lassa and Hantavirus.
Oral and aerosol admin
hemolytic anemia, bone marrow suprression in high doses.
upper airway irritation
monoclonal antibody against RSV
given IM for compromised children.
Mechanism: Blocks attachment, penetration and uncoating of influenza AAAAAAA.
Clinical use: Prophylaxis mainly, but may reduce duration of flue symptoms by 1-2 days.
CNS: Nervousness, insomnia, seizures in OD!
Causes atropine like peripheral effects and livedo reticularis.