The document summarizes the pharmacology of antiviral drugs. It discusses the stages of viral replication and types of viruses. It then classifies antiviral drugs into different categories based on the virus they target such as anti-herpes viruses, anti-influenza viruses, anti-hepatitis viruses, and anti-retroviruses. For each category of antiviral drugs, it provides examples of drugs, their mechanisms of action, pharmacokinetics, uses, and adverse effects in concise detail. The document concludes by citing the reference used.

1. Submitted By
Naveen K L
Dept. Of Pharmacology
Srinivas College Of Pharmacy
Valachil, Mangalore
1
Chemotherapy of Antiviral Drugs

2. Contents:
• Introduction
• Stages of viral replication
• Types of viruses
• Classification
• Pharmacology of antiviral drugs
• References
2

3. • Viruses are Ultramicroscopic obligatory intracellular
parasite resistant to antibiotic but susceptible to
interferon's.
• Structurally viruses consisting of core of nucleic acid which
is surrounded by Proteinous coat called Capsid, the entire
structure is covered by external lipid membrane called
Envelop.
• The nucleic acid may be DNA or RNA. Depending on DNA
or RNA they can classified as DNA virus or RNA virus.
• Viruses can replicate only inside the host cells and they
utilize the host enzyme systems, therefore targeting of the
virus selectively is very difficult.
Introduction
3

4. Stages of Viral Replication
Free virus particle
Adsorption or attachment to host cell
Penetration
Uncoating
Replication
Assembly & maturation
Release of Virions
4

5. Types of Viruses:
5

6. What are antivirals ?
Antivirals are a class of medication used specifically for treating viral
infections rather than bacterial ones. Most of the antivirals are used for
specific viral infections, while a broad-spectrum antiviral is effective
against a wide range of viruses.
6

7. Classification:
1) Anti-Herpes virus
Idoxurudine, Trifluridine, Acyclovir, Valacyclovir, Famciclovir,
Ganciclovir, Valganciclovir, Foscarnet.
2) Anti-Influenza virus
Amantidine, Rimantadine, Zanamivir, Oseltamivir.
3) Anti- Herpatitis virus or Nonselective antiviral drugs
 Primarily for Hepatitis B:
Lamivudine, Adefovir, Tenofovir.
 Primarily for Hepatitis C:
Ribavirin, Interferon α
7

8. 4) Anti- Retrovirus
 NRTIs
Zidovudine, Stavudine, Lamivudine, Abacavir, Emtricitabine, Tenofovir.
 NNRTIs
Nevirapine, Delaviridine, Efavirenz
 Protease Inhibitor
Ritonavir, Lopinavir, Amprenavir, Saquinavir, Atazanavir, Indinavir.
 Entry (Fusion) Inhibitor
Enfuvirtide
 CCR5 receptor Inhibitor
Maraviroc
 Integrase Inhibitor
Raltegravir 8

9. Anti herpes virus:
• Drugs active against herpes group of DNA virus
• HSV-1, HSV-2, VZV and Not Active Against CMV (Cytomegalovirus)
a) Acyclovir:
 Synthetic, deoxiguanosine analogue, antiherpes activity.
 Mainly effective against HSV-1, HSV-2, Epstein Barr virus & less
effective in VZV.
 Drug requires virus specific enzyme for conversion to the active
metabolite that inhibits DNA synthesis and viral replication.
9

10. Mechanism of action:
10

11. Pharmacokinetic ADRs Uses
• Its used in genital
infection caused by
HSV-2.
• Mucocutaneous
infection caused by
HSV-1
• Used for the
chicken pox caused
by VZV.
• In herpetic whitlow
(Nail-bed infection)
• In herpetic
encephalitis.
• Only 20% oral dose of
Acyclovir is absorbed.
• Administration done by
orally, iv, topically.
• Little plasma Concentration
and widely Distributed
through out the Body
having 50% CSF
concentration.
• Metabolite are excreted in
urine in Unchanged form,
both by GF & TS.
• Plasma t1/2 2-3 hrs.
• Local irritation
may occurs from
topical
application.
• Headache,
Diarrhoea,
Nausea, vomiting,
malaise.
• Transient renal
dysfunction may
occur.
• Rashes, sweating,
emesis, and fall in
BP
11

12. Anti influenza virus:
12
• Four antiviral drugs are available for the prevention and treatment of
influenza infections: Oseltamivir, Zanamivir, Rimantadine and
Amantadine.
• Oseltamivir and Zanamivir are neuraminidase inhibitors, acting against
both influenza A and B infections.
• Rimantadine and amantadine block the M2 channel of influenza A virus

13. Anti influenza virus:
Amantidine:
• Chemically synthetic tricyclic amine unrelated to any nucleic acid precursor,
but inhibits the replication of influenza A virus.
• The antiviral activity of Amantidine is strain specific i.e. influenza B isn’t
affected while Influenza A is affected.
• Amantidine acts as both antiviral and anti- Parkinson's drug.
Mechanism of action: Amantidine inhibits the early step in viral replication.
Inhibits the replication of each of the subtypes of influenza A virus, i.e. H1N1,
H2N2 & H3N2. it has minimal or no activity against influenza B Bcz this virus
contain different protein other than M2 in its membrane (act as ion channel).
13

14. Pharmacokinetic:
• Amantidine is well absorbed
orally and excreted unchanged
in urine over 2-3 days
• 67% protein bound
• T ½ is 16 hrs.
Uses:
Amantidine indicated for the
prophylaxis and treatment of
infection caused by numerous
strains of influenza A virus.
Adverse effects:
• Nausea, dizziness and insomnia.
• Less frequent side effects
depression, anxiety,
hallucination, confusion,
anorexia, dry mouth,
constipation, ataxia,
hypotension, headache,
diarrhoea and irritability.
14

15. Anti- Herpatitis virus /
Nonselective Antiviral drugs
• Several antiviral drugs are relatively virus nonselective and inhibit viruses
belonging to different classes; even cover both DNA and RNA viruses.
• While hepatitis B virus (HBV) is a DNA virus which, like retroviruses, can
integrate into host chromosomal DNA to establish permanent infection, the
hepatitis C virus (HCV) is a RNA virus, which does not integrate into
chromosomal DNA, does not establish noncurable infection, but frequently
causes chronic hepatitis
15

16. • Adefovir:
• Adefovir is a monophosphate analogue of AMP which is active against HBV and
some other DNA as well as RNA viruses, but is used only for hepatitis caused by
HBV.
• On entering cells, adefovir is phosphorylated to the diphosphate which has high
affinity for HBV DNA polymerase compared to host cell DNA polymerase. This
enzyme is inhibited and adefovir itself gets incorporated in the viral DNA
resulting in termination of the DNA chain.
• Tenofovir:
• It is a monophosphate nucleotide related to AMP, which is active against HBV as
well as HIV.
• Tenofovir released from hydrolysis of the prodrug is diphosphorylated by cellular
kinases into tenofovir diphosphate which preferentially inhibits HBV DNA
polymerase and HIV-reverse transcriptase.
• Affinity for host DNA-polymerase is very low. It also gets incorporated in the viral
DNA to cause chain termination.
16

17. Interferon α:
• Interferon's are naturally occurring low molecular weight glycoprotein
cytokines produced by host cells in response to viral infections.
• They have nonspecific antiviral as well as other complex effects on the
immunity and cell proliferation.
• IFNs binds to specific cell surface receptors and affects viral replication at
multiple steps, viz. viral penetration, synthesis of mRNA, assembly of viral
particles and their release, but the most widespread effects is direct or
indirect inhibition of viral protein synthesis.
• Interferon inhibits DNA and RNA viruses, but they are host specific.
• 3 types of human IFNs are known and they having antiviral activity. Only
IFNα2A & IFNα2B produced from rDNA technology and are clinically used.
17

18. 18

19. Pharmacokinetic :
• Administered by i.m/s.c. injection
distributed to tissue. Its degraded
mainly in liver and kidney, and remains
detectable in plasma for 24 hrs.
Uses:
 Chronic hepatitis B
 Chronic hepatitis C
 AIDS related Kaposi's sarcoma
 Condyloma acuminata
 Chronic myeloid leukaemia, follicular
lymphoma, cutaneous T-Cell lymphoma
and multiple myeloma
Adverse effects:
 Flu like symptoms --- fatigue, aches
and pains. Malaise, fever, dizziness,
anorexia, nausea, taste and visual
disturbances.
 Neurotoxicity---- numbness,
neuropathy, mental depression,
altered behaviour, tremor, sleepiness
and rarely convulsions.
 Thyroid dysfunction (both hypo and
hyper).
 Hypotension, transient arrhythmias,
alopecia and renal dysfunction.
 Dose dependent neutropenia,
thrombocytopenia
19

20. Anti retrovirus drugs:
• These are drugs active against HIV which is a retrovirus. They are
useful in prolonging and improving the quality of life and postponing
complications of AIDS or AIDS- related complex (ARC), but don’t cure
the infection.
• The clinical efficacy of antiretrovirus drugs is monitored primarily by
plasma HIV-RNA assay & CD4 lymphocyte count carried out at
regular intervals.
20

21. NRTIs: Zidovudine
• It’s a thymidine analogue (Azidothymidine, AZT).
• Prototype drug of NRTIs.
• Zidovudine triphosphate selectively inhibits the viral reverse transcriptase
in preference to cellular DNA polymerase.
Cellular
AZT AZT-monophosphate AZT-triphosphate
thymidine HIV
kinase reverse transcriptase
5’ …………………… AZT
3’ ……………………………………………5’
21

22. Pharmacokinetic Adverse effects
• Oral absorption of AZT Anaemia, neutropenia
is rapid, but BA ˞65%. Nausea, anorexia, headache
metabolised in liver by Abdominal pain, insomnia
Glucuronide conjugation Myalgia, myopathy
Unchanged and metabolite Pigmentation of nails
Are excreted via urine. Lactic acidosis, convulsion
PPP is 30% and CSF level Hepatic megaly
Is 50% Encephalopathy
Crosses placenta and is
found
In milk, t1/2 1 hrs.
Uses
• Active against HIV-
1,HIV-2, and human T-
cell lymphotropic
viruses.
• Mainly used in
treatment of HIV,
decreases rate of
progression and
prolongs survival.
• Prevents mother to
new-born
transmission of HIV.
• Used as antiretroviral
therapy.
22

23. NNRTIs: Nevirapine (NVP) and Efavirenz (EFV)
• These are nucleoside unrelated compounds which directly inhibits HIV
reverse transcriptase without need for intracellular phosphorylation .
• Locus of action on enzyme is different and they are non-competitive
inhibitor.
• They are more potent than AZT on HIV-1,but don’t inhibits HIV-2.
Reverse
Viral RNA transcription Proviral DNA
transcriptase
NVP or EFV 23

24. Pharmacokinetic
• NVP is well absorbed orally, is extensively metabolised mainly by CYP3A4 and
lesser extent to CYP2B6, with a t1/2 30 hrs.
• Oral absorption of EFV is 50% but t1/2 48 hrs. completely metabolized mainly
by CYP2B6 and smaller fraction by CYP3A4
Adverse effects:
NVP: rashes are common, followed by nausea, fever and headache.
potentially its hepatotoxic.
EFV: headache, rashes, dizziness, insomnia and variety of neuropsychiatric
symptoms. Since its teratogenic, contraindicated in pregnancy and in
women likely to get pregnant.
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25. Retroviral Protease Inhibitor:
• Protease is an enzyme encoded by HIV is involved in the production of
structural protein and enzymes (including RT and Integrase) of the virus from
large viral polyprotein synthesised in infected cells.
• The polyprotein is broken into various functional components by the
protease enzymes.
• its act at late step in HIV replication i.e. maturation of new viral particle
when the RNA genome acquires core protein and enzymes.
• PIs bind to active site of protease molecule, interfere with cleaving function.
• Eg: Atazanavir, Indinavir, Nelfinavir, Saquinavir, Ritonavir, Lopinavir
25

26. Pharmacokinetic:
• Oral bioavailability of PIs is variable (IDV&RTV 65%, NFV >20%, SQV 15%) and
their plasma t1/2 ranges from 2-8 hrs.
• All are extensively metabolized mainly by CYP3A4, except NFV which is
substrate of CYP2C19, all PIs are potent inhibitor of CYP3A4 (RTV & LPV) and
some others are inducer.
Adverse effects:
GIT intolerance, asthenia, headache, dizziness, limb and facial tingling,
numbness and rashes, dyslipidaemia, abdominal obesity, fatigue, diarrhoea,
etc.
26

27. Entry or Fusion Inhibitor:
Enfuvirtide:
• This HIV derived synthetic peptide acts by binding to HIV-1 envelope
transmembrane glycoprotein (gp41) which is involved in fusion of viral and
cellular membranes.
• Fusion of two membrane is thus prevented and entry of the virus into the
cell is blocked. Its not active against HIV-2.
• Adm s.c. twice daily, the injections are painful and cause local nodules
/cysts.
27

28. Integrase inhibitor:
Raltegravir:
• The HIV- Proviral DNA transcripted in the cytoplasm of the host
cell translocate to the nucleus along with an Integrase enzyme.
• The HIV- Integrase nicks host chromosomal DNA and integrate
the Proviral DNA with it .
• Orally active drug that blocks this step by inhibiting the
Integrase enzyme.
• Its active against both HIV-1 & HIV-2
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29. 29

30. • KD Tripathi. Essential of MEDICAL PHARMACOLOGY, 8th edition. New
dehli;Jaypee brothers medical publisher;2019 p 798-812.
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