2. Virus :Obligate parasite
Virus particles (virions)
consist of following parts:
• Genetic material (DNA or
RNA).
• Protein coat (capsid) that
surrounds nucleic acid.
• Envelope (contains lipids
and lipoproteins) that
surrounds the capsid when
virus is outside a cell.
2
8. Anti Herpes Drugs
Herpesviridae family- HSV-1, HSV-2, VZV, CMV
Mouth, face skin, esophagus , brain----HSV-1
Genitals , rectum, skin , hands, meninges----HSV-2
Arrest DNA synthesis by inhibiting viral DNA polymerase .
Most of them prodrugs
Require Viral and Host cellular enzymes ( eg. Thymidine
deoxyguanosine kinase ) to phosphorylate them into active
triphosphate form
Common mechanism of resistance is alteration in viral enzymes
9
10. Acyclovir
• Synthetic analogue of guanosine
• Valacyclovir is a prodrug
Acyclovir monophosphate is phosphorylated to
triphosphate , gets incorporated into Viral DNA and inhibits
replication.
HSV thymidine kinase
DNA polymerase
Chain termination
Suicide inactivation
Spectrum: HSV-1, HSV-2, VZV
Never totally cure
11
11. • Advantage:
– No hematotoxicity, no myelosupression
– Treatment of herpes encephalitis
• Resistance :
– Absence or partial production of TK
– Altered TK specificity
– Altered viral DNA polymerase
• Adverse effects :
–
–
–
–
–
PEG base topical effects
Oral- nausea , vomiting , diarrhoea and headache
Dose dependent renal impairment , crystallie nephropathy
Neurological – lethargy , confusion , tremors
Rash , itching and phlebitis at injection site
12
12. Ganciclovir
• Similar to acyclovir
• First phosphorylation viral specific, TK in HSV,
Phosphotransferase (UL97) in CMV
• Triphosphate form inhibits viral DNA polymerase
and causes chain termination
• HSV, VZV, CMV reitinitis in HIV patients
• Dose limiting hematotoxicity, mucositis , fever,
rash , crystalluria
• Seizures in overdose
13
13. Foscarnet
Inorganic pyrophosphate analog inhibitory for
herpes and HIV
• Not an antimetabolite
• Interacts directly with Viral DNA polymerase
or HIV reverse transcriptase
• Blocks binding site of pyrophosphate and
inhibits cleavage
• IV
14
15. Anti-influenza agents
• Amantadine/ rimantadine
–
–
–
–
–
–
–
–
–
–
–
–
Tricyclic amines
Low concentration inhibits replication
Rimantadine more active , also for Trypanosoma brucei
Inhibit attachment, penetration and viral uncoating
M2 protein inhibition
Potentiate acid pH induced changes in hemaggluttin during
intracellular transfer
Minor Dose related GIT and CNS effects
Atropine like
Livedo reticularis
Insomnia
Loss of appetite
Teratogenic
16
16. Oseltamivir/zanamivir
– Absorbed rapidly and cleaved to active
carboxylate
– Selective inhibitor of vial neuraminidase and leads
to viral aggregation and reduced spread
– Nausea , abdominal discomfort—given with food
– Nasal and throat irritation
– Flu like
– Influenza A and B
17
17. Ribavirin
• Monophosphorylated form inhibits IMP
dehydrogenase and as a result depletes intracellular
nucleotide reserves.
• Triphosphate inhibits viral RNA polymerase and end
capping of viral RNA
• Used as an adjunct to IFN in HCV infection
• Management of respiratory syncytial virus
• Lassa fever
• Hematotoxic
• Upper airway irritation
• Teratogenic
18
18. Anti hepatitis agents
• Adefovir dipivoxil
– Acyclic phosphonate
nucleotide of adenosine
monophosphate
– Adefovir diphosphate is
competitive inhibitor of
DNA polymerase and
reverse transcriptase
– Chain terminator
– Chronic HBV
– Lamivudine resistant
HBV strains
– Reduced carnitine
– Dose related
nephrotoxicity/tubular
dysfunction
– Headache , abdominal
discomfort, diarrhoea ,
asthenia
– Hepatotoxicity ,lymphoid
toxicity
19
19. Interferons
• Potent cytokines
• Antiviral, immunomodulating and
antiproliferative
• Synthesised by host cells
• Types –
– α, β- all cells, stimulate MHC antigen
– γ - T lymphocytes / NK cells
• Pegylated interferon
• Inhibit protein synthesis , activate
endoribonuclease
20
23. Reverse Transcriptase Inhibitors
• NRTIs :
Inactive until phosphorylated by human cellular
kinases
Used together with protease inhibitors
• NNRTIs:
– Not prodrugs
– No myelosupression
– Efavirenz, nevirapine
24
33. HIV Postexposure Prophylaxis (PEP)
Contact with blood /fluid or blood transfusion
Sharp injury or needle stick of HIV infected
NRTIs for 28 days/ with triple therapy (dual
NRTIs plus a boosted PI)
34
34. Prevention of mother-to-childtransmission
• Start Zidovudine (AZT) from 28 weeks or as
soon as possible thereafter, be provided with
single-dose Nevirapine (NVP) when entering
labour, and be given AZT+3TC for one week
following delivery
35
35. Quick Review of Antiviral Agents
•
•
•
•
Anti herpetics
Anti influenza agents
Anti hepatitis viral infections
Anti retroviral drugs
36
