The document discusses antiviral drugs, including their classification, mechanisms of action, and examples. It describes how viruses lack cellular structures and can only replicate inside host cells. Antiviral drugs target specific stages of the viral lifecycle, such as viral entry, DNA/RNA synthesis and replication, and viral release. Common classes include purine and pyrimidine nucleotides, adamantane derivatives, and phosphorus derivatives. Examples like acyclovir, amantadine, and idoxuridine are summarized in terms of their structures, mechanisms of action inhibiting viral enzymes or DNA replication, and clinical uses for treating viruses like influenza, herpes, and cytomegalovirus.

1. ANTIVIRAL
DRUGS

2. CONTENTS
INTRODUCTION
STRUCTURE OF VIRUSES
LIFE CYCLE OF VIRUSES
CLASSIFICATION OF ANTIVIRAL DRUGS
MODE OF ACTION
STRUCTURAL ACTIVITY RELATIONSHIP
FEW DRUGS(SYNTHESIS MODE OF ACTION AND USES)
SUMMARY
REFERENCE

3. ANTI-VIRALDRUGS:-
 Anti viral drugs are the class of medication used
specifically for treating viral infections. Viruses are
obligate intracellular parasites, smallest of all self
replicating organisms, able to pass through filter
that retain the smallest bacteria. Virus conduct no
metabolic process on their own. They invade the
host cell which may be bacteria, animal or plant
cell.
 Viruses are small infectious agents that replicates
only inside the living cells of other organisms.
 They lack both cell wall and cell membrane and they
do not carry out metabolic process

4. STRUCTURE OFVIRUS:-
 Virus doesn’t possess cell
wall.
 It consists of one or more of
linear or helical strands of
either DNA or RNA,enclosed
in the shell of protein known
as capsid.
 The capsid is composed of
several sub units known as
capsomers.
 In certain cases,capsid may
be surrounded by an outer
protein or lipoprotein
envelop.

5. LIFECYCLEOFVIRUS:-
1.Adsorption:-Attachment of virus to the host cell.
2.Penetration:-Penetration of virus into the host
cell.
3.Uncoating:-The genetic material of viral genome(DNA/RNA)passes
into the host cell, leaving the capsid covering outside the cell.
4.Transcription:-Production of viral m-RNA from viral genome.
5.Translation:-Viral genome enters the cytoplasm or nucleoplasm
and utilizes the host nucleic acid for the synthesis of new viral
protein and also for the production of more viral genome. The viral
protein modifies the host cell and allows the viral genome to
replicate by using host and viral enzyme. In this stage, the cell is
irreversibly modified and eventually killed.

6. 6.Assembly:-New viral
coat protein assembles
into capsid and viral
genomes.
7.Release:-Release of the
mature virus from the cells
by budding process or by
rupture of the cell and the
process is repeated in fresh
host cell.Since the host cell
machinery is totally utilised
for the production of new
virions,the normal cell
function ceases at the time
of production.

7. CLASSIFICATION

8. CLASSIFICATIONOFANTIVIRALAGENTS:-
The anti viral agents may be divided into the following categories
based on their chemical structure:-
A. Purine nucleotides:-
Acyclovir,Ganciclovir,Vidarabine,Valaciclovir,Penciclovir
B. Pyrimidine nucleotides:-
Trifluridine,Idoxuridine
C. Admantane derivatives:-
Amantadine,Rimantadine,Somantadine,Tromantadine
D. Phosphorus derivatives:-
Foscarnet

9. 1.ADMANTANEDERIVATIVES:-
a)Amantadine b)Rimantadine c)Somantadine d)Tromantadine

10. 2.PURINENUCLEOTIDES:-
a)Acyclovir b)Ganciclovir

11. c)Vidarabine d)Valaciclovir

12. 3.PYRIMIDINENUCLEOTIDES:-
a)Trifluridine b)Idoxuridine

13. 4.PHOSPHORUSDERIVATIVES:-
Foscarnet

14. Viral attachment and
entry are blocked by:
• Enfuvirtide(HIV)
• Maraviroc(HIV)
• Docosanol(HSV)
• Palivizumab (RSV)
Uncoating are blocked by:
• Amantadine (influenza)
• Rimantadine(influenza)
Nucleic acid synthesis
are blocked by:
• Nucleoside reverse
transcriptase
Inhibitors NRTI
(HIV,HBV)
• Non-Nucleoside
reverse transcriptase
Inhibitors NNRTI
(HIV)
• Acyclovir (HSV)
• Foscarnet(CMV)
Protein processing
are blocked
by:
• Protease inhibitors (HIV)
• Ritonavir, Nelfinavir
Viral release are blocked by:
• Neuraminidase
inhibitors(Influenzas)

15. STRUCTURAL ACTIVITY RELATIONSHIP
A. ADMANTANE DERIVATIVES:
i. N-ALKYL AND N,N-DIALKYL DERIVATIVES OF
AMANTADINE EXHIBIT ANTIVIRAL ACTIVITY
SIMILAR TO THAT OF AMANTADINE
HYDROCHLORIDE.
ii. N-ACYL DERIVATIVES OF AMANTADINE SHOW
REDUCED ANTIVIRAL ACTIVITY EXCEPT GLYCYL
DERIVATIVES.
iii. REPLACEMENT OF THE AMINO GROUP WITH OH,
SH, CN OR HALOGEN PRODUCED INACTIVE
COMPOUNDS.
B. IODOXURIDINE
i. REPLACEMENT OF IODINE AT THE POSITION 5`
WITH TRIFLURIDINE CAN BE ADMINISTERED AT
LOWER DOSE FREQUENCY AND GIVES
METABOLICALLY STABLE PRODUCT THAN
IDOXURIDINE.

16. C. ACYCLOVIR:
i. To improve the bioavailability of acyclovir side chain –OH converted to L-
valylester (10 times more than ACV) (Valacyclovir)VACV.
ii. It does not contains any free –OH group, so the molecules cannot be
phosphorylated prior to conversion. The prodrug (VACV) is rapidly converted to
ACV in humanhydrolase present in liver and gut wall. VACV has no intrinsic
antiviral activity.

17. iii. Addition of a –CH2 in the side chain of acyclovir give a opposite
behavior. This addition effects the activity spectrum and safety
profile. E.g. Gancyclovir.
iv. Replacement of C=O with –NH2 in acyclovir afford good water
solubility but poorly adsorbed and are not metabolised efficiently.
E.g. Desciclovir
v. Addition of a phosphonate group in the side chain of ACV reduces
five times less active compound than ACV against HSV invitro.
vi. 2-Amino is substituted with 3,5-dichlorobenzyl group gives
inhibitory action of HSV-1 (Herpes Simplex virus), DNA synthesis,
but display minimal antiviral selectivity and effectively inhibit cell
DNA.
vii.Addition of a phosphonate group in the side chain of GCV
equipotent and less toxic that GCV but it causes renal tubular
damage.
viii.C=O of side chain by methylene groups (pencyclovir) give high
selective activity agaist herpes laboratory strain, it is far better
substrate for enzyme than ACV but less potent that ACV.
ix. The diacetyl ester prodrug of 6-deoxy PCV (Femcyclovir) gives high
blood level of PCV (about 70% after oral administration.

18. Amantadine (1-aminoadamantane)
and its methyl derivative inhibit
the uncoating of the viral RNA
within the infected host cells thus
preventing its replication.
Specifically targets a protein called
M2 (an ion channel).Inactive
against influenza B, which lacks
M2
Amantadine:

19. PROPERTIES&USES:-
Amantadine is a white,odourless,crystalline powder with a
bitter taste,freely soluble in water.It is effective in the
prophylaxis and therapy of infection caused by influenza-A
and is active against a number of DNA and RNA virus in
vitro.It may block either the assembly of influenza-A virus
or the release of viral nucleic acid in the host cell.
The drug is well absorbed from the GIT is not metabolised
and is excreted by the kidney.
Dose related adverse effects include
confusion,hallucinations,seizures &
coma.

20. They are hydrophobic
amines (weak organic
bases) with clinical
against influenza A only.
Their specificity stems
from their ability to bind
to block the proton
channel formed by the
M2 matix protein.
Can reduce severity of
illness if started within
48 hrs of onset of
symptoms .
MECHANISM OF ACTION

21. SYNTHESISOFAMANTADINE:-
Adamatane
1-bromo-adamatane
1-acetylamino-
adamatane
Amantidine

22. ACYCLOVIR
(9-[2(hydroxyethoxy)methyl]9h guanine)
 It is the prototypic antiherpetic therapeutic
agent. Herpes simplex virus (HSV) types 1
and 2,varicella-zoster virus (VZV) (i.e.
chickenpox and shingles).
 Acyclovir has a nucleoside-like structure
 It lacks the complete sugar ring.
 In virally infected cells, it is
phosphorylated to form a triphosphate
which is the active agent, and so acyclovir
is a prodrug
 Acyclovir triphosphate prevents DNA
replication in two ways.
 Firstly, it can bind to DNA polymerase and
inhibit it.
 Secondly, the drug acts as a chain terminator

23. acyclovir MonoPO4
guanosine mono Po4 kinase
Acyclovir triPO4
Acyclovir triPO4 compete for deoxy guanine triPO4 and hence it
competetively inhibit DNA polymerase.
It also incorporate with viral DNA chain during DNA
synthesis. Because Acyclovir triPO4 lacks 3’OH group of
cyclic sugar, it terminates further elongation of DNA chain.
MECHANISM
ACYCLOVIR
thymidine kinase

24. SYNTHESIS

25. USESOFACYCLOVIR:-
It is a drug of choice in both prophylaxis and treatment of
herpes simplex virus,particularly type-1 including chronic and
recurrent mucocutaneous herpes in the immunologically
impaired host,primary and secondary genital herpes and herpes
simplex encephalitis.Cells infected with herpex simplex
phosphorylate the drug to yield a cycloguanosine
triphosphate,which preferentially inhibits viral DNA polymerase.

26. Its 5 trifluromethyl 2’deoxy uridine
MECHANISM
Trifluridine mono PO4 irreversibily inhibits thymidylate synthase
Trifluridine tripo4 cometetively inhibits thymidine triPO4
incorporation into DNA by DNA polymerase
TriPO4 form is incorporated into cellular DNA, crating fragile &
poorly functions DNA
Uses: keratoconjuctivities & epithelial keratitis due to HSV 1&
HSV2
TRIFLURIDINE

27. SYNTHESISOFTRIFLURIDINE:-

28. SYNTHESISOFIDOXURIDINE:-
Idoxuridine

29. USESOFIDOXURIDINE:-
IDOXURIDINE IS MAINLY USED FOR THE TOPICAL
TREATMENT OF HSV INFECTION OF EYELID,CONJUCTIVA &
CORNEA AND APPROVED AS OPTHALMIC OINTMENT OR
SOLUTION.EPITHELIAL INFECTIONS RESPOND MUCH
BETTER THAN STROMAL INFECTIONS.

30. SUMMARYMOAOFANTIVIRALAGENTS:-

31. REFRENCES
i. Fundamentals of Medicinal
Chemistry,Gareth Thomas
ii. Wilson and Gisvold’s Textbook of
ORGANIC MEDICINAL AND
PHARMACEUTICAL CHEMISTRY
(12th edition)
iii. https://www.ncbi.nlm.nih.gov/pubmed/16
134757
iv. https://www.ncbi.nlm.nih.gov/pmc/articles
/PMC438 0148/