What are viruses?

2. ANTI-VIRALS
Faizan Akram
Roll # 152
Final Professional (Eve)
Faizanbwp@Hotmail.com

3. Declaration
1. Medicinal Chemistry by Ashutosh Kar (6th Edition).
2. Textbook of Organic Medicinal and
pharmaceutical chemistry by Wilson & Gisvold’s (12th
Edition).
3. Lippincott Illustrated Reviews: Pharmacology (6th
edition).
4. Foye's Principles of Medicinal Chemistry (6th
Edition).

4. Presentation Agenda
What are viruses?
Viral Replication
Classification of antivirals drugs
Mechanism of Action
Acyclovir
Ribavirin
Tromantadine Hydrochloride

5. What are viruses?
VIRUSES:
Single or double stranded DNA or RNA enclosed
in a protein – CAPSID
Obligate intracellular parasite
Replication depends on synthetic processes of
the host cell.
Antiviral drugs must either block entry or exit
from cell or be active inside the host cell

6. Viral replication
Adsorption and penetration into susceptible host
cells.
Un coating of viral nucleic acid
Synthesis of early regulatory proteins
Synthesis of RNA or DNA
Synthesis of late regulatory proteins
Assembly (maturation) of viral particles
Release from cells

8. Classification of antiviral drugs
A) Substances that inhibit early stages of viral
replication.
B) Substances that interfere with viral nucleic acid
replication.
C) Substances that affect translation on cell
ribosome's.
Antiviral drugs are broadly classified on the basis of their
specific mode of action

10. Acyclovir
 A widely used antiviral with main implications in
the treatment of herpes.
 Seen as a “new age” in antiviral therapy, Gertrude
Elion, its creator, was given the Nobel prize for
medicine in 1988.
 It is a nucleoside analogue and prevents viral
replication in infected cells.
 Extremely selective and low in toxicity.

11. Structure of acyclovir

12. Mechanism of action
There are three mechanisms by which ACV show antiviral
activity:
1) 1st mechanism
ACV ACV-monophosphate ACV-
diphosphate ACV-triphosphate
 1: viral thymidine kinase2: normal cellular enzyme,
 2: guanosine monophosphate kinase
 3: normal cellular enzyme ,guanosine monophosphate
kinase
 ACV- triphosphate competitively inhibits the viral DNA
polymerase

13. 2nd mechanism: viral DNA polymerase is
competitively inhibited by ACV-TP with lower median
inhibition concentration (IC50) compared to cellular
DNA polymerase.
 ACV-TP is incorporated into viral DNA chain during
DNA synthesis because ACV-TP lacks 3`-hydroxyl
group of cyclic sugar, it terminates further
elongation of DNA chain.
Mechanisms:

14. 3rd mechanism:
as preferential uptake of ACV by herpes infected cells
as compared to uninfected/normal cells resulting in
higher concentration of ACV-TP and leading to high
therapeutic index.
Mechanisms:

16. Therapeutic Uses
Effective against the following:
1. Herpes simplex virus type I (HSV-1)
2. Herpes simplex virus type II (HSV-2)
3. Varicella zoster virus (VZV)
4. Epstein-Barr virus (EBV)
5. Cytomegalovirus (CMV) -- least activity
6. ACV is active against most species in herpes
virus family.
7.Decreasing order of activity includes:
HSV-1 > HSV-2 > VZV > EBV > CMV

17. Ribavirin
Ribavirin have broad spectrum activity, it is purine
nucleoside analogue with modified base and D-ribose
sugar moiety
PROPERTIES:
It is white, crystalline and polymorphic solid
Its soluble in water and chemically stable

18. Chemical structure of Ribavirin

19. Mechanism of action
 Ribavirin nucleoside is bio activated by viral and host cellular
kinase to produce Ribavirin Monophosphate (RMP) and
Ribavirin Triphosphate (RTP)
 RMP: inhibit conversion of inosine monophosphate (IMP) to
Xanthine Monophosphate (XMP)
 XMP: is required for guanosine triphosphate (GTP) synthesis
 RTP: inhibits viral RNA polymerases, it also prevent the end
capping of viral mRNA by inhibiting guanyl-N`-methyl
transferases

20. Therapeutic Uses
 Ribavirin inhibit replication of wide variety of RNA
and DNA viruses including:
o Orthomyxoviruses
o poxviruses
o Paramyxoviruses
o Arenaviruses
o adenoviruses
o Herpes viruses
o rhinoviruses
o influenza (type A and B)

21. Tromantadine HCL
 Tromantadine is an anti-viral agent which is active
against herpes simplex virus.
 It is available in a topical gel under the trade name
Viru-Merz.
 Its performance is similar to acyclovir.
 Like rimantadine and amantadine, it is an derivative
of adamantine.

22. Chemical structure of
Tromantadine HCL

23. Mechanism of action
 Tromantadine inhibits early and late events in the
viral replication cycle.
 It inhibits penetration of viruses as well as un coating
of virions.
 It changes the glycoproteins of host cells, therefore
impeding the absorption of virus