1. DR.RAHUL
10/5/2013
DR RAHUL KUNKULOL
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2. Viruses are made up of core genome of
nucleic acid contained in a protein shell
called Capsid
 Surrounded by lipoprotein membrane called
envelope (Genome + Capsid + Envelope = Virion)
Viruses are obligate intracellular parasite ie.
do not have a metabolic machinery of their
own – uses host enzymes
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3. • Certain viruses multiply in the cytoplasm
but others do in the nucleus
• Some viruses have unique enzymes for
DNA/RNA synthesis or protein cutting
in virus assembly.
• Most multiplication take place before
diagnosis is made
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4. • DNA viruses
• Adenoviruses (upper respiratory infections)
• Herpes simplex (genital herpes)
• Hepadna virus (hepatitis B)
• Cytomegalovirus (CMV)
• Varicella (chickenpox) and varicella-zoster
• Smallpox
• RNA viruses : Influenza A and B
• RNA retroviruses : Human immunodeficiency virus (HIV)
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5. Adsorption to and penetration of
susceptible cells.
Synthesis of early, nonstructural proteins.
Synthesis of RNA or DNA.
Synthesis of late, structural proteins
Assembly of viral particles and release
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Viral uncoating
Nucleoside analogs
Non-nucleoside polymerase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Protease inhibitors
Neuraminidase inhibitors

9. Many antiviral drugs are Purine or
Pyrimidine analogs.
Many antiviral drugs are Prodrugs.
They must be phosphorylated by viral or
cellular enzymes in order to become
active.
Anti-viral agents inhibits active replication
The viral growth resumes after drug
removal.
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10. Current anti-viral agents do not eliminate
non-replicating or latent virus
Effective host immune response remains
essential for the recovery from the viral
infection
Clinical efficacy depends on achieving
inhibitory conc. at the site of infection
within the infected cells
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11. :(Herpes, CMV, HIV, R.Syncitial)
 Purine analogues
Acyclovir Valacyclovir
Ganciclovir Valganciclovir
Penciclovir Famciclovir
Cidofovir (c) Adefovir (a)
Vidarabine (a)
 Pyrimidine analogues
 Idoxuridine
 Trifluridine
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12. Foscarnet (Direct inhibitor of DNA polymerase and RT)
Ribavirin Fomivirsen
(Influenza)
Amantadine Rimantadine
Zanamavir Oseltamivir
Interferon-alpha (Hepat. B&C, Herpes)
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13. Figure 20.16a
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14. • Valacyclovir is a prodrug of Acyclovir with
better bioavailability.
• Famciclovir is hydrolyzed to Penciclovir and
has greatest bioavailability.
• Penciclovir is used only topically whereas
Famciclovir can be administered orally.
• All are guanine nucleoside analogs.
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16. 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.
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17. A Guanine analogue with antiviral for Herpes group only
Acyclovir AcycloGMP AcycloGTP
Thymidine kinase Cellular kinases
Viral 200x affinity
of mammalian
1. Inhibits viral DNA polymerase selectively
2. Incorporated into DNA and terminates synthesis
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18. Active against
HSV-1 (Labial and
ocular infection)
HSV-2 (Genital
infection)
Varicella-zoster
infections
 Epstein barr virus
Resistance :
HSV and varicella
zoster
Deficiency in
thymidine kinase
activity
Changes in virus
directed enzymes
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20. • Primary disease :
• Acyclovir 5% ointment 6 times a day for 10
days
• Late & severe cases: 400 mg TDS orally for
10 days
• Recurrent disease:
• Iv infusion 5mg/kg over 1 hr repeated 8 hrly
for 10 days
• Followed by suppressive treatment with oral
acyclovir
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• Mucocutaneous :
• Remains localized to lips and gums
(Acyclovir skin cream)
• H.Simplex encephalitis
• 10 mg /kg /8hr iv acyclovir for 10 days
• H. Simplex keratitis (HSV–I)
• Acyclovir eye ointment 5 times a day for
3days

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Chickenpox :
Oral 400mg TDS for 7 days
Herpes zoster infections
Acyclovir less active

23. • Oral :
• Headach, N/v, diarrhea, vertigo
• IV :
• Phlebitis, rash , hypotention
• Nephrotoxicity
• Reversible neurological manifestations
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24. • Mechanism like Acyclovir
• Active against all Herpes viruses including
CMV
• Low oral bioavailability given I.V.
• Drug of choice for CMV infections:
retinitis, pneumonia, colitis…
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25. Bone marrow suppression
(leukopenia 40%, thrombocytopenia 20%)
CNS effects
(headache, behavioral, psychosis, coma,
convulsions)
1/3 of patients have to stop because of adverse
effects
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26. Guanine
Acyclovir Ganciclovir
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DR RAHUL KUNKULOL
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27. Approved for the treatment of CMV retinitis in
immunocompromised patients
Nucleoside analog of cytosine
 Gets converted to only cidofovir diphosphate
and inhibit viral DNA polymerase
 It inhibits viral DNA synthesis
Available for IV, Intravitreal inj, Topical
Nephrotoxicity is a major disadvantage.
Uses : CMV retinitis
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28. Adenosine analogue
Converted by cellular kinases to active diphosphate
Inhibits Hepatitis B virus DNA polymerase
Gets incorporated into DNA causes Chain
termination
Use: Chronic hepatitis B
AE : Nephrotoxicity, lactic acidosis,
hepatomegaly.
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29. Adenine nucleoside analogue
Convert to Ara-A triphosphate and inhibit DNA
polymerase
Active against HSV and vaccina virus
› Treatment of HSV encephalitis and herpetic keratitis
 Poor solubility, given i.v. with big volume of
fluids (2.5 L) ⇒ risk of fluid overload
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30.  GI
 Bone marrow
 Hypokalemia
 Inappropriate ADH secretion;
 Psychosis; painful neuropathy;
 Not a drug of choice for anything :
 Replaced by Acyclovir because of toxicity and
problems in administration.
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31. • Active against HSV and VZV
• First pyrimidine analogue used as antiviral.
• It is iodinated derivative of deoxyuridine.
• MOA same as acyclovir
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32. • Topical use for treatment of HSV infections
of the eyelid, cornea and skin.
• Only indication-
Herpes simplex kerato-conjunctivitis
• High toxicity :
• Bone marrow depression
• Due to incorporation of idoxuridine into host
cell DNA
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33. • 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
• Very poor oral bioavalibility so given slow iv.
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34. • CMV retinitis and other CMV infections
instead of Ganciclovir.
• H simplex resistant to Acyclovir
• H. simplex in AIDS patients
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35. • Nephrotoxicity (25%) most common ADR
• Hypocalcaemia (chelates divalent cations)
• Others: Hypokalemia,
Hypomagnesaemia
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36. Inhibit replication of both DNA and
RNA viruses
Triphosphate inhibits RNA polymerase
Anemia due to hemolysis and BM
suppression
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37. Ribavirin is the drug of choice for:
• RSV bronchiolitis and pneumonia in
hospitalized children (given by aerosol)
Ribavirin is an alternative drug for:
• Influenza, Parainfluenza, Measles virus
infection in immunocompromised
patients
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38. • Is a Oligonucleotide
• Primarily an anti CMV agent
• Binds to mRNA and inhibit synthesis of
immediate early proteins needed for
replication
• Injected intravitreally for : CMV retinitis in
patients of AIDS
• A/E: Iritis, Vitreitis.
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40. • Chemically a tricyclic amine not related to any
nucleotide
• Inhibit penetration of virus to cells ,the uncoating of
certain virus and viral replication.
• M2 protein which acts as ion channell appears to be
its one of the target.
• Prevent diseases caused by influenza A
• Treatment of Parkinson’s disease
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41. • GI upset
• Headache
• Nervousness
• Postural hypotension, ankle edema
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42. • Inhibit neuraminidase enzyme of influenza
• Enzyme essential for release of virus
• Examples: zanamivir and oseltamivir
• Zanamivir administered via inhalation
administered orally
• Oseltamivir is converted to O. carboxylate
(oral bioavalibility 80%)
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43. • Therapeutic Use
• Treatment of acute uncomplicated Influenza A
(H1N1 virus, swine flu) : Oseltamivir 75mg BD
• Prevention : 75mg OD
• Adverse effects
• N/V, Bronchospasm and abnormal
respiratory function
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44. • Three classes of interferons – α , β, γ
• α and β interferons: produced by all the
cells in response to viral infections
• γ interferon : produced only by T
lymphocyte and NK cells in response to
cytokines – immune regulating effects
• γ has less anti-viral activity compared to α
and β interferon
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45. Induction of the following enzymes:
A protein kinase which inhibits protein
synthesis
An oligo-adenylate synthase which leads to
degradation of viral mRNA
A phosphodiesterase which inhibit t-RNA
The action of these enzymes leads to an
inhibition of translation
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46. • Interferon prevent spread of viruses to new cells
(Viral hepatitis)
• Natural products of the immune system in viral
infections
• Antiviral, anticancer and immuno-modulating
• Toxicity: flu-like syndrome, BM suppression; CNS
• Use :Hepatitis B and C
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47. Antivirals Spectrum
Acyclovir HSV-1, HSV-2, VZV, Shingles.
Ganciclovir CMV
Famciclovir Herpes genitalis, shingles
Cidofovir CMV
Adefovir HBV
Idoxuridine,
Trifluridine
Herpetic keratoconjunctivitis
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48. Antivirals Spectrum
Foscarnet HSV, CMV in AIDS
Ribavirin RSV, Parainfluenza
Fomivirsen CMV retinitis in AIDS
Amantidine,
Rimantidine
Influenza A Virus
Oseltamivir H1N1 influenza
Interferon HBV, HCV
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49. Virus Diseases
Drug(s) of
choice
Alternative
drugs
Inf. A
Influenza Amantadine Rimantadine
RSV
Pneumonia,
bronchiolitis
Ribavirin
(aerosol)
HSV Genital herpes Acyclovir Foscarnet
Keratitis
Conjunctivitis
Trifluridine
Idoxuridine
Vidarabine
Encephalitis Acyclovir
Neonatal HSV
infection
Acyclovir Vidarabine
Herpes infections in
immuno-
compromised host
Acyclovir Foscarnet
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50. In normal host No therapy
Immunocompromised
host, or pregnancy Acyclovir Foscarnet
CMV Retinitis Ganciclovir Foscarnet
HCV
InterferonsHepatitis B
Hepatitis C
VZV
CMV
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HBV

51. • Guanosine analogue
• Competitively inhibits viral DNA
polymerase
• Approved by FDA in march 2005 for
treatment of chronic hepatitis B
• Oral bioavailibility : 95%
• AE : Headach, fatigue, NV
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52. • Neuramidase inhibitor
• Approved in 2009
• For emergency treatment of hospitalised
patients of H1N1 infection
• Used iv for patients resistant to
Oseltamivir, zanamivir….
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