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1. Anti viral agents
Dr. Himanshu Khatri
Email: himanshubkhatri@yahoo.co.in

2. • Antibacterial agents are not effective against
viruses, as the targets for them are absent in
viruses
• Even for viruses, chemotherapy is available for
selected viruses
• Chemotherapy is also not effective against viruses
which become latent in cells (e.g. herpesviruses).
These viruses are usually susceptible to antiviral
agents when they are not in latent stage

3. • Inhibition of early events
• Inhibition of viral nucleic acid synthesis
• Inhibition of integrase
• Inhibition of cleavage of precursor
polypeptides (protease inhibitors)
• Inhibition of viral protein synthesis
• Inhibition of release of virus

4. Inhibition of early events
• Amantadine and rimantidine
• Enfuvirtide
• Maraviroc
• Palivizumab

5. Amantadine and rimantadine
• Blocks the M2 matrix
protein in the virus
prevents uncoating of virus
inside the cell
• Absorption and penetration
are not affected
• Effective only against
influenza A
• Not effective against
influenza B and C
• Rimantadine has fewer side
effects than amantidine

6. Enfuvirtide
• Blocks gp41 of HIV
• Prevents fusion of viral envelope with cell
membrane (‘fusion inhibitors’)

7. Maraviroc
• Some strains of HIV
bind to CCR-5 receptor
on the cell surface,
through their gp120
• Maraviroc binds to CCR-
5, and prevents binding
of gp120 to CCR-5

8. Palivizumab
• Binds to the fusion protein of respiratory
syncytial virus (RSV), and thus prevents its
binding to respiratory tract cells

9. Inhibition of viral nucleic acid synthesis
• Inhibitors of Herpesviruses
• Inhibitors of Retroviruses
• Inhibitors of Hepatitis B virus
• Inhibitors of Hepatitis C virus
• Inhibitors of Other Viruses

10. Inhibitors of Herpesviruses
• Nucleoside inhibitors
1. Acyclovir
2. Ganciclovir
3. Cidofovir
4. Vidarabine
5. Idoxuridine
6. Trifluridine
• Nonnucleoside inhibitors
1. Foscarnet

11. • Nucleoside inhibitors:
1. Analogues of nucleosides
2. Inhibit DNA polymerase of one or more
members of herpesvirus family

12. Acyclovir
• Guanosine analogue
• It is in inactive form activated only
in virus infected cells by virus-
encoded thymidine kinase to
acyclovir monophosphate
therefore, non-toxic to non-infected
cells
• Acyclovir monophosphate is
converted into diphosphate and then
into triphosphate by cellular kinases
• Acyclovir triphosphate is
incorporated into growing
herpesvirus DNA chain, and acting as
premature chain terminater, inhibits
viral DNA polymerase
• Viral DNA polymerase is inhibited to a
greater extent than cellular DNA
polymerase

13. • Active against HSV-1, HSV-2, and VZV only, as
they can be activated by virus-encoded
thymidine kinases of these viruses
• Ineffective against CMV and Epstein-Barr virus
• Ineffective against viruses which are latent in
cells
• Recently, resistance has been noted against
acyclovir

14. Derivatives of acyclovir
• Valaciclovir
• Penciclovir
• Famciclovir

15. Ganciclovir
• Guanosine analogue
• It is in inactive
formactivated into
active form by a CMV-
encoded
phosphokinasetherefor
e, active only against CMV
• Recently, resistance has
emerged due to mutation
in UL97 gene, which
codes for phosphokinase
• Valganciclovir is a
derivative of ganciclovir

16. Cidofovir
• Cytosine analogue
• Effective against CMV and human
papillomavirus infection

17. Vidarabine
• Adenine analogue
• Mechanism of activation and action similar to
acyclovir
• Effective only against HSV-1
• Less effective and more toxic than acyclovir

18. Idoxuridine and trifluridine
• Thymidine analogues
• Mechanism of activation and action similar to
acyclovir
• But it is incorporated in normal cell DNA as
effectively as viral DNA therefore, too toxic
for systemic usetherefore, used only
topically

19. Non-nucleoside inhibitor-Foscarnet
• Pyrophosphate analogue
• Binds DNA polymerase at pyrophosphate
cleavage site and prevents removal of phosphate
from nucleoside triphosphates (dNTP)this
prevents addition of next dNTP in the elongating
strand of DNA
• It inhibits DNA polymerases of all herpesviruses
• It can be used for treatment of acyclovir-resistant
mutants of HSV-1 and VZV

20. Inhibitors of retroviruses
• Nucleoside reverse transcriptase inhibitors
(NRTIs)
• Non-nucleoside reverse transcriptase
inhibitors (NNRTIs)

21. Nucleoside reverse transcriptase
inhibitors (NRTIs)
• Nucleoside analogues
• Bind to the reverse
transcriptase of HIV,
and cause chain
termination
• Bind to the reverse
transcriptase of HIV
preferentially to the
DNA polymerase of
human cells

22. Nucleoside reverse transcriptase
inhibitors (NRTIs)
1. Zidovudine
2. Lamivudine
3. Emtricitabine
4. Didanosine
5. Stavudine
6. Abacavir
7. Tenofovir

23. Non-nucleoside reverse transcriptase
inhibitors (NNRTIs)
• NOT nucleoside
analogues
• Bind to the active site of
reverse transcriptase and
cause of conformational
change to the enzyme
• Not used as
monotherapy, as resistant
mutants emerge rapidly
• Typically used in
combination with one or
two NRTIs

24. Non-nucleoside reverse transcriptase
inhibitors (NNRTIs)
1. Nevirapine
2. Delavirdine
3. Efavirenz
4. Etravirine
5. Rilpivirine

25. Inhibitors of Hepatitis B virus
• Are usually nucleoside analogues, which bind to
the DNA polymerase (reverse transcriptase) of
Hepatitis B virus
• Examples include:
1. Lamivudine (already discussed earlier)
2. Tenofovir (already discussed earlier)
3. Adefovir (adenosine analogue)
4. Entecavir (guanosine analogue)
5. Telbivudine (thymidine analogue)

26. Inhibitor of other viruses
• Ribavirin
1. Nucleoside analogue
2. Used in treatment of respiratory syncytial
virus (RSV) infections, influenza B infections,
and treatment of Hepatitis C infections

27. Inhibitors of integrase
• Integrase is an enzyme
in HIV which causes
integration of viral DNA
into host cell DNA
• Examples of integrase
inhibitors are:
1. Raltegravir
2. Dolutegravir
3. Elvitegravir

28. Inhibition of cleavage of precursor
polypeptides (protease inhibitors)
• Protease is an enzyme in HIV
which cleaves several non-
functional precursor
polypeptides into functional
proteins
• These inhibitors bind to this
protease enzyme, thereby
preventing the cleavage of
precursor polypeptides
functional proteins are not
formed replication is halted
• However, they cannot cure
infection, as proviral DNA is
not targeted

29. Protease inhibitors
• Not used as monotherapy, as resistant
mutants emerge rapidly
• Typically used in combination with one or two
NRTIs

30. Protease inhibitors
• Saquinavir
• Indinavir
• Ritonavir
• Lopinavir
• Atazanavir
• Tipranavir
• Amprenavir
• Fosamprenavir
• Darunavir
• Nelfinavir

31. Protease inhibitors of Hepatitis C virus
• Boceprevir
• Simeprevir
• Telaprevir

32. Inhibition of viral protein synthesis-
Interferons
• Interferons are proteins produced by host cells on
induction by viral or non-viral inducers
• It belongs to the class of cytokines
• Interferon itself has no direct action, but acts on
other cells, making them refractory to viral
infection. It can also have immuno-modulatory
and anti-proliferative actions on certain cells.
• Interferon inhibits translation, and possibly
transcription, of viral proteins by the host cell

33. • The activity of interferon is not virus specific,
and may confer protection against unrelated
viruses also
• Interferon production is increased at higher
temperatures, and inhibited by steroids

34. • Alpha interferon (IFN-α): produced by
leucocytes
• Beta interferon (IFN-β): produced by
fibroblasts and epithelial cells
• Gamma interferon (IFN-γ): produced by T-
lymphocytes, and is more concerned with
immunomodulatory and anti-proliferative
functions

35. • They are inactivated by proteases
• They are poorly antigenic, and hence are
difficult to detect by serological methods
• They are non-toxic
• Potency of IFN is expressed as International
Units (IU) per ml

36. Inhibition of release of virus
• Neuraminidase is an enzyme in influenza virus,
which is essential for release of daughter virions
from the infected cells
• Neuraminidase inhibitors block this enzyme
daughter virions are not releasedother cells are
not infected infection is limited
• Examples include zanamivir and oseltamivir
• They are effective against both influenza A and B
viruses
• They are also effective against amantadine-
resistant strains of influenza virus

37. Thank you

38. Questions?