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)
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
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.
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
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.
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.
