1. Anti Viral

2. Introduction to Viruses
• Viruses are composed of nucleic acid,
protein capsid, and host membrane
containing virus proteins.
• Virus are obligate parasite
Mammalian  Mammalian virus
Insect
 arbovirus
Plant
 Plant virus
Bacteria
 Bacteriophage

3. • Viruses live inside host cells and use many
host enzymes.
• viruses have core genome of nucleic acid
either DNA or RNA.
•DNA viruses
 Adenoviruses (upper respiratory infections)
 Hepadnaviruses
 Herpes virus(HSV-1,HSV-2,VZV,CMV)
 Poxvirus ( small pox)
 Papilloma viruses (warts)

4. •RNA viruses
 Arborvirus-yellow fever
 Arenaviruses- meningitis
 Bunya viruses- encephalitis
 Coronaviruses- URI
 Influenza A and B
 Paramyxoviruses – Measles, mumps
 Rhabdoviruses- Rabbies
 Human immunodeficiency virus (HIV)

5. Viral Replication(DNA)

6. RNA viruses replication
RNA viruses  replication
in the cytoplasam.
Own enzyme to synthesis
mRNA
mRNA translated as Viral
proteins
genomic RNA

7. RNA virus replication (Influenza)

8. Anti viral therapy
• Restricted spectrum
• No standardized in-vitro susceptibility tests
• Most inhibit replication.
• Cure depends on host immune system to
eradicate.
• If patients are immunocompromized, may
have recurrences.
• Drugs need to be activated by viral and cellular
enzymes before exerting antiviral effect.
• Activity of enzymes and concentration of
substrates will influence the efficacy.

9. Mechanisms of Action of
Antiviral Drugs
•Targets include
• Viral penetration
• uncoating
• Nucleoside analogs
• Non-nucleoside polymerase inhibitors
• Neuraminidase inhibitors

10. Classification
• DNA polymerase inhibitors
― Purine Nucleoside Analogues:
Acyclovir
Ganciclovir
Famiciclovir
Valacyclovir Penciclovir
Cidofovir
– Pyrimidine Nucleoside Analogues:
Idoxuridine
– Non nucloside
Foscarnet
• Inhibitors of viral penetration, uncoating
Amantadine Rimantadine
• m-RNA Synthesis inhibitors
Ribvirin
Fomivirsen
• Neuraminidase Inhibitors
Zanamivir
Oseltamivir
• Immunomodulators
Immunoglobulins
Imiquimod
Interferns
Palivizumab

11. Nucleoside Analogues
General Mechanism of Action
1. Taken up by cells
2. Converted by viral and cellualr enzymes to
the triphosphate form
3. The triphosphate form inhibits:
•
•
•
DNA polymerase
Reverse transcriptase
RNA polymerase
4. Or it may get incorporated into growing
DNA leading to abnormal proteins or
breakage.

12. Antiviral Drugs
Nucleoside and Nucleotide Analogs

13. Analogs Block DNA Synthesis
Figure 20.16b,
c

14. Acyclovir
and Valacyclovir (prodrug, better availability)
A Guanine analogue
Acyclovir
AcycloGMP
Thymidine kinase
AcycloGTP
Cellular kinases
Viral 200x affinity
of mammalian
1.
2.
Inhibits viral DNA polymerase selectively
Incorporated into DNA and terminates synthesis
Resistance:
Toxicity:
Use:
1. ↓ activity of thymidine kinase 1. Encephalopathy
1. H. simplez I and II
2. altered DNA polymerase
2. Renal Insuficiency 2. H. zoster and Varicella,
not good for CMV

15. Pharacokinetics
• Oral
• 20-30% BV highly susceptible infection
• Wide distribution
• 20% plasma binding
• 90% excreted in unchange from in urine
• T ½-3-4hr, but in renal failure- 20hrs.

16. Spectrum and clinical use
Highly effective against
• HSV-1
• HSV-2 genital herpes
• Varicella zoster (Chickenpox)
Parenteral  mucocutaneous HSV
VZV, H.Simplex encephalitis
Ointment  early genital herpes
Ophthalmic  herpes keratoconjunctivitis

17. Adverse effects
• Oral 3-6months use headache,
diarrhoea, nausea, vomiting.
• IV – Phelbitis, rash, mild hypotension
• renaltoxicity
• DI- Cyclosporine nephro toxicity
• Probencid inhibits renal excretion

18. Acyclovir
Ganciclovir
Guanine

19. Ganciclovir:
• Hydroxy methylated analogue of
acyclovir
• Poor BV, IV , t ½- 3-4hrs
• Use parenteral serious CMV (accu.100 folds)
• ADR:- Myelosupression, neutropenia,
anaemia, Teratogenic , carcinogenic

20. Valacyclovir
• L- Valine ester of acyclovir
• Mechanism and clinical use same
• It require less oral dose
• More effective than acyclovir  Zoster
• No IV formulation

21. Idoxuridine
• First pyrimidine antimetabolite, used as
antiviral drug.
• MOA –incorporate in DNA →formed
faulty DNA which breaks down easily
→synthesis of wronge viral protein.

22. Use
• Only topical ophthalmic use
• H. simplex keratoconjunctivitis.
• Dose – one drop of 0.1% solution
hourly during day time and two hourly
during night time.
• In acute stage- 0.5% eye ointment four
hourly for 3 weeks.
• Side effect – ocular irritation, lid odema,
photophobia.

23. Foscarnet
• An inorganic pyrophosphate analog
• Active against Herpes (I, II, Varicella , CMV),
including those resistant to Acyclovir and
Ganciclovir.
• Direct inhibition of DNA polymerase and RT
• Nephrotoxicity (25%) most common ADR
• Hypocalcemia (chelates divalent cations)
• Others: hypokalemia, hypomagnesemia
• Use: CMV retinitis and other CMV infections
instead of ganciclovir. H simplex resistant to
Acyclovir.

24. NON-SELECTIVE
ANTIVIRAL DRUG
RIBAVIRIN• Has broad spectrum antiviral activity.
• Oral bioavailability-50%
• MAO: Inhibits viral RNAp
• USE- 1. Influenza –A,B
2. Measles in immunocompramised pt.,
• Route  aerosol  to treat Respiratory syncitial
virus
• DOSE- 200MG/QID

25. ADVERSE EFFECT
• ANAEMIA
• HAEMOLYSIS.
• IRRITATION TO MUCOSA &
BRONCHOSPASM DUE TO
AEROSOL.

26. Inhibitors of viral penetration
and uncoating
• Amantadine and Rimantadine
• Synthetic tricyclic amines
• Active against Influenza-A
• MAO:- Inhibit viral M2 protein
• t ½- 17-25hr.

27. Neuraminidase inhibitors
• Oseltamivir, Zanamivir
• Oral  Oseltamivir carboxylate
• 80% BV
• t ½- 8hrs.
• Effective against influenza
• ADR: Zanamivir- bronchospasm, Nasal
discomfort

28. Immunomodulators
• Interferons:• Enhanced production of cytokines
• Glycoprotiens produced by body cells
after viral infections.
• TYPES :
1. ALPHA (α)Leucocytes
2. BETA (β) fibroblasts
3 . GAMMA (γ)  T-lymphocytes

29. • IFN- α, β  potent anti viral effects
• IFN- γ antiviral & immuno modulatory
• IFNs Bind to cell surface receptors 
viral penetration , m-RNA synthesis,
assembly of virions.