2. Introduction to Viruses
ā¢ Viruses are composed of nucleic acid,
protein capsid, and host membrane
containing virus proteins.
ā¢ Virus are obligate parasite
Mammalian ļ Mammalian virus
Insect
ļ arbovirus
Plant
ļ Plant virus
Bacteria
ļ Bacteriophage
3. ā¢ Viruses live inside host cells and use many
host enzymes.
ā¢ viruses have core genome of nucleic acid
either DNA or RNA.
ā¢DNA viruses
ļ¼ Adenoviruses (upper respiratory infections)
ļ¼ Hepadnaviruses
ļ¼ Herpes virus(HSV-1,HSV-2,VZV,CMV)
ļ¼ Poxvirus ( small pox)
ļ¼ Papilloma viruses (warts)
4. ā¢RNA viruses
ļ¼ Arborvirus-yellow fever
ļ¼ Arenaviruses- meningitis
ļ¼ Bunya viruses- encephalitis
ļ¼ Coronaviruses- URI
ļ¼ Influenza A and B
ļ¼ Paramyxoviruses ā Measles, mumps
ļ¼ Rhabdoviruses- Rabbies
ļ¼ Human immunodeficiency virus (HIV)
8. Anti viral therapy
ā¢ Restricted spectrum
ā¢ No standardized in-vitro susceptibility tests
ā¢ Most inhibit replication.
ā¢ Cure depends on host immune system to
eradicate.
ā¢ If patients are immunocompromized, may
have recurrences.
ā¢ Drugs need to be activated by viral and cellular
enzymes before exerting antiviral effect.
ā¢ Activity of enzymes and concentration of
substrates will influence the efficacy.
9. Mechanisms of Action of
Antiviral Drugs
ā¢Targets include
ā¢ Viral penetration
ā¢ uncoating
ā¢ Nucleoside analogs
ā¢ Non-nucleoside polymerase inhibitors
ā¢ 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:
ā¢
ā¢
ā¢
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. ā 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
ā¢ Oral
ā¢ 20-30% BVļ highly susceptible infection
ā¢ Wide distribution
ā¢ 20% plasma binding
ā¢ 90% excreted in unchange from in urine
ā¢ T Ā½-3-4hr, but in renal failure- 20hrs.
16. Spectrum and clinical use
Highly effective against
ā¢ HSV-1
ā¢ HSV-2 genital herpes
ā¢ Varicella zoster (Chickenpox)
Parenteral ļ mucocutaneous HSV
VZV, H.Simplex encephalitis
Ointment ļ early genital herpes
Ophthalmic ļ herpes keratoconjunctivitis
19. Ganciclovir:
ā¢ Hydroxy methylated analogue of
acyclovir
ā¢ Poor BV, IV , t Ā½- 3-4hrs
ā¢ Use parenteralļ serious CMV (accu.100 folds)
ā¢ ADR:- Myelosupression, neutropenia,
anaemia, Teratogenic , carcinogenic
20. Valacyclovir
ā¢ L- Valine ester of acyclovir
ā¢ Mechanism and clinical use same
ā¢ It require less oral dose
ā¢ More effective than acyclovir ļ Zoster
ā¢ No IV formulation
21. Idoxuridine
ā¢ First pyrimidine antimetabolite, used as
antiviral drug.
ā¢ MOA āincorporate in DNA āformed
faulty DNA which breaks down easily
āsynthesis of wronge viral protein.
22. Use
ā¢ Only topical ophthalmic use
ā¢ H. simplex keratoconjunctivitis.
ā¢ Dose ā one drop of 0.1% solution
hourly during day time and two hourly
during night time.
ā¢ In acute stage- 0.5% eye ointment four
hourly for 3 weeks.
ā¢ Side effect ā ocular irritation, lid odema,
photophobia.
23. Foscarnet
ā¢ An inorganic pyrophosphate analog
ā¢ Active against Herpes (I, II, Varicella , CMV),
including those resistant to Acyclovir and
Ganciclovir.
ā¢ Direct inhibition of DNA polymerase and RT
ā¢ Nephrotoxicity (25%) most common ADR
ā¢ Hypocalcemia (chelates divalent cations)
ā¢ Others: hypokalemia, hypomagnesemia
ā¢ Use: CMV retinitis and other CMV infections
instead of ganciclovir. H simplex resistant to
Acyclovir.
26. Inhibitors of viral penetration
and uncoating
ā¢ Amantadine and Rimantadine
ā¢ Synthetic tricyclic amines
ā¢ Active against Influenza-A
ā¢ MAO:- Inhibit viral M2 protein
ā¢ t Ā½- 17-25hr.