Antiviral drugs are a class of medications used to treat viral infections by inhibiting the replication or growth of viruses in the body. These drugs work by targeting specific components of a virus, such as the viral enzymes, proteins, or nucleic acids, and disrupting their ability to infect or replicate inside host cells. This can help reduce the severity of symptoms, prevent complications, and speed up recovery. There are many types of antiviral drugs available, including: 1. Nucleoside or nucleotide analogues: These drugs mimic the structure of the nucleosides or nucleotides needed for viral replication, thereby interfering with virus replication. 2. Protease inhibitors: These drugs block the activity of viral proteases, which are enzymes that are required for the replication and assembly of some viruses. 3. Interferons: These drugs are naturally occurring proteins that help the immune system fight viral infections by boosting the body's antiviral response. 4. Neuraminidase inhibitors: These drugs block the activity of viral neuraminidase, an enzyme that is required for the release of virus particles from infected cells. 5. Fusion inhibitors: These drugs block the fusion of viral and host cell membranes, which is an essential step in viral entry and replication. Antiviral drugs can be used to treat a variety of viral infections, including influenza, HIV/AIDS, hepatitis B and C, herpes, and Ebola. However, the effectiveness of these drugs can vary depending on the specific virus and the stage of infection. Antiviral drugs may also have side effects, and it is important to consult with a healthcare provider before taking them.

1. Anti-Viral
Presented By: Vaishnavi Gohri
F.Y. M. Pharm ( Pharmacology )
Roll No: 04

2. INTRODUCTION:
• Replicates inside the host cells
• Viruses are intracellular parasites
• They lack both a cell wall and a cell membrane
• Size are between 20nm to 400nm
• The viruses are tiny particles have 3 part only:
1. DNA or RNA carrying genetics information
2. Protein coat that protect the gene
3. Envelop of lipids which surrounds the lipid coat
• They can infect various parts of the body, including the respiratory, digestive, & nervous system
• Common cold, flu, chickenpox, & measles are commonly causing viral infection

4. Steps Involved in causing
Viral Infection
(Life cycle)
1. Binding of virus
2. Fusion with host cell membrane
3. Penetration
4. Uncoating occurs
5. Early protein synthesis occurs
6. Replication of viral nucleic acid
7. Late protein synthesis & Processing
8. Packaging & Assembly
9. Release of Virions
lytic cycle or
lysogenic cycle to
reproduce

5. • Many antiviral drugs are purine or pyrimidine analogues
• Preventing reproduction and spreading in the body.
• Targeting genetic material or the enzymes of virus needed for replication
• Used to treat infections such as HIV, hepatitis B and C, herpes & flu
• Some antiviral drug work by boosting the immune system
• Depending upon the type of virus & the severity of the infection
ANTIVIRAL DRUGS:

6. Steps of replication inhibited by different Anti-viral Drugs

7. Classification of Non-retroviral Drugs
CLASS DRUGS
Anti-Herpes virus drugs
Idoxuridine, Trifluridine, Acyclovir, Valacyclovir,
Famciclovir, Ganciclovir, Valganciclovir, Cidofovir,
Foscarnet, Fomivirsen
Anti-Influenza virus drugs
Amantadine, Rimantadine, Oseltamivir,
zanamivir, Peramivir
Anti-Hepatitis virus drugs
a) For hepatitis B
b) For hepatitis C
Lamivudine, Etanercept, Adefovir, Dipivoxil,
Tenofovir, Telbevudine
Ribavirin, Interferon α, Sofosbuvir, Simeprevir

8. CLASS DRUGS
Nucleoside reverse transcriptase inhibitors
(NRTIs)
Zidovudine, Didanosine, stavudine,
Lamivudine, Abacavir, Tenofovir
Nonnucleoside reverse transcriptase inhibitors
(NNRTIs) Nevirapine, Efavirenz, Delavirdine
Protease inhibitors
Ritonavir, Atazanavir, Indinavir,
Nelfinavir, Saquinavir, Lopinavir
Entry ( Fusion ) inhibitor Enfuvirtide
CCR5 receptor inhibitor Maraviroc
Integrase inhibitor Raltegravir
Classification of Anti-Retroviral Drugs

9. • Herpes simplex viruses (HSV-1 and HSV-2)
• Varicella-zoster virus (VZV)
• Epstein – Barr virus (EBV)
• Cytomegalovirus (CMV)
CLASS: Anti-herpes virus drugs
These are drugs active against the Herpes group of DNA viruses which includes
Idoxuridine, Trifluridine, Acyclovir, Valacyclovir,
Famciclovir, Ganciclovir, Valganciclovir,
Cidofovir, Foscarnet, Fomivirsen

10. Virion host shutoff - vhs
HSV-1: Oral herpes or cold
sores
HSV-2: Genital herpes
Pathogenesis

11. Acyclovir
Acyclovir ( Prodrug )
Acyclovir monophosphate
Acyclovir Triphosphate
(Analogue of dGTP)
Inhibits herpes virus DNA
polymerase competitively
Gets incorporated in viral DNA &
stops lengthening of DNA strand
Terminated DNA elongation & inhibits DNA polymerase irreversibly
It is an deoxyguanosine analogue
Treatment for herpes viruses, genital herpes, cold sores, shingles & chickenpox infections
thymidine kinase

12. Pharmacokinetics:
 Absorption: 20% of an oral dose of acyclovir is absorbed.
 Distribution: little plasma protein bound, CSF concentration that is 50% Penetrates cornea.
 Metabolism: In liver.
 Excretion: unchanged in urine, both by glomerular filtration and tubular secretion
 plasma half life is 2-3 hours
 Renal impairments must have dose reduction

13. Used in treatment of
Genital Herpes Mucocutaneous
Encephalitis
keratitis
Herpes zoster
Chickenpox

14.  Genital Herpes simplex:
 Caused by type-2 virus; can be treated by topical, oral or parenteral acyclovir
 Treatment with 5% ointment is applied locally 6 times a day for 10 days
 Mucocutaneous H. simplex:
 Type - 1 virus disease
 Infection of lips and gums; Spreading lesions may be treated with 10 day
H. simplex encephalitis:
 Type-1 virus, Acyclovir 10 to 20mg / kg / 8 hr given i.v. for more than 10 days

15.  H. simplex (type I) keratitis:
 Acyclovir eye ointment acts slower than idoxuridine drops, blindness can be prevented
Herpes zoster:
 The varicella-zoster virus is less susceptible to acyclovir.
 In severe cases: 10 mg/kg/8 hr i.v for 7 days
Chickenpox:
 Acyclovir (15 mg/kg/day i.v. for 7 days) is the drug of choice.
 Reduces fever, eruptions, hastens healing and prevents visceral complications.

16. 1. After topical: Stinging and burning sensation
2. After Oral: headache, nausea and some CNS effects
3. After Intravenous: Rashes, sweating and fall in BP occur.
4. Includes tremors, lethargy, disorientation, hallucinations, convulsions and coma
5. No teratogenic potential has been noted.
Side Effects of Acyclovir
Adverse Effects of Acyclovir

17. Ganciclovir
 Nucleoside analogue, used to prevent & treat infections caused by the cytomegalovirus (CMV).
 Inhibiting the viral DNA polymerase
 Prevents the virus from multiplying and spreading in the body
 Uses:
 Treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS)
 Prevention of CMV disease in solid organ transplantation and bone marrow transplantation recipients.
 Side effects:
 Fever, chills, headache, nausea, vomiting, diarrhea, rash, anemia, leukopenia, thrombocytopenia, increased
liver enzymes, and kidney damage, seizures, confusion, and hallucinations may occur.
 Dose:
 5 mg/kg intravenously twice daily for 14 to 21 days
 Followed by a maintenance dose of 5 mg/kg administered once daily.

18. Valacyclovir:
 It is a prodrug of acyclovir
 Blocking the action of the virus DNA polymerase enzyme, which is necessary for viral replication
 This prevents the virus from multiplying and spreading within the body
 Treat infection of herpes simplex virus (HSV), varicella-zoster virus (VZV), and Epstein-Barr virus
 Famciclovir:
 It is a prodrug that is converted into penciclovir, which works in a similar way to acyclovir
 Valganciclovir:
 It is a pro-drug of ganciclovir
 Preventing the replication of the CMV virus by inhibiting its DNA polymerase.
 When valganciclovir is absorbed by the body, it is metabolized into ganciclovir
 Which then acts as the active antiviral agent.
Other Drugs

19.  Treat flu infections caused by influenza
 Work by blocking ability to enter or
replicate within host cells
 Mainly used antiviral drugs include:
 Oseltamivir, zanamivir & peramivir these
are neuraminidase inhibitors
 Amantadine & rimantadine viral M2 ion
channels inhibitors
 Baloxavir & marboxil are RNA
polymerase inhibitors
 Some influenza strains have developed
resistance to certain antiviral drugs
Class: Anti influenza virus drugs

20. Mechanism of Anti influenza drugs

21. It is tricyclic amine
Mechanism of Action:
 It inhibits replication of influenza A virus (a myxovirus)
 Inhibit viral M2 ion channels to prevent influenza viral replication
 H5N1 (avian influenza/bird flu) and H1N1 (swine flu) strains of influenza A are resistant
 It act on step (possibly uncoating) as well as at a late step (viral assembly) in viral replication
Pharmacokinetics:
 Oral bioavailability: 50-90%
 It has ability to cross BBB whereas rimantadine not
 Excretion in Urine
Amantadine

22. Resistance:
 Caused due to mutation of amino acid substitutions in the M2 protein.
Uses:
1. Prophylaxis of influenza A2:
 Amantadine and vaccination are given in combination as it not interfere with antibody response.
 Amantadine not recommended in UK, either for prophylaxis or for treatment of influenza.
2. Parkinsonism:
 Due to anticholinergic property used in treatment of parkinsonism.

23. Adverse effects
CNS effects: Nausea, anorexia, insomnia, dizziness
Psychological effect: nightmares, lack of mental concentration, rarely hallucinations
Local effect: Ankle edema occurs due to local vasoconstriction.
 Epilepsy
 CNS disease
 Gastric ulcer
 Pregnancy
Contraindicated

24.  It is an ester prodrug, hydrolyzed to the active form oseltamivir carboxylate
 Newer anti-influenza virus drug is a sialic acid analogue with broad spectrum
 oral bioavailability of ~ 80%
 t½ of 6–10 hours
 Acts by inhibiting influenza virus neuraminidase enzyme
 Which is needed for release of progeny virions from the infected cell
 Prophylactic use for 5–10 days prevents illness in contacts of influenza patients.
Oseltamivir
Zanamivir
 Administered by inhalation as a powder due to very low oral bioavailability
 t½ of 2–5 hours
 The inhaled powder can induce bronchospasm in some individuals, this may be severe in asthma
 Headache, dizziness, nausea and rashes are mild and infrequent side effects

25. Class: Anti-hepatitis virus

26.  It is a monophosphate analogue of Adenosine mono phosphate.
 Active against Hepatitis B Virus and some other DNA as well as RNA viruses
 Mechanism of Action:
 Adefovir phosphorylated to Adefovir diphosphate
 Having high affinity for HBV DNA polymerase compared to host cell DNA polymerase
 Inhibition of enzyme & adefovir itself gets incorporated in the viral DNA
 Resulting termination of the DNA chain showing antiviral activity
 Pharmacokinetics:
 Oral bioavailability: 59%
 Half life: 7hr
 No clinical relevant drug-drug interaction
 Change in dosing for renal impairment patients required
Adefovir & dipivoxil (Primarily for hepatitis B)

27. Uses:
 Chronic hepatitis B, including lamivudine resistant cases & having concurrent HIV infection
Side effects:
 Sore throat, headache, weakness, abdominal pain and flu syndrome.
 Nephrotoxicity occurs at higher doses and in those with preexisting renal insufficiency.
 Lactic acidosis is a risk in patients receiving anti-HIV drugs

28.  Low molecular weight glycoprotein
cytokines produced by host cells in
response to viral infections
 TNF α, IL-1 and some other inducers
 Three types of human IFNs (α, β and y)
are known to have antiviral activity
 IFNα2A and IFNα2B produced by
recombinant technology administered by
i.m or s.c injection
Interferon α : (Primarily for hepatitis C)

29. Mechanism of Action:
Interferon receptors are JAK -STAT tyrosine protein kinase receptors
Activation phosphorylate cellular proteins
Migrate to nucleus and induce transcription of interferon induced proteins
Resulting in affect viral replication at multiple steps
Viral penetration, synthesis of viral mRNA, assembly of viral particles and their release
It is direct or indirect suppression of viral protein synthesis exert antiviral effects

30. Uses:
Chronic hepatitis B Chronic hepatitis C
AIDS-related Kaposi's sarcoma
Condyloma acuminata
H. simplex, H. zoster and CMV

31.  Flu-like symptoms-fatigue, aches, pains, fever, dizziness, anorexia, nausea, taste and visual disturbances
 Neurotoxicity-numbness, neuropathy, altered behaviour, mental depression, tremor, sleepiness, rarely convulsions
 Myelosuppression: dose dependent neutropenia, thrombocytopenia
 Thyroid dysfunction (hypo as well as hyper)
 Hypotension, arrhythmias, alopecia and liver dysfunction
Adverse effect:

32.  This purine nucleoside analogue has broad-spectrum antiviral activity
 Including that against influenza A and B
 It is mono & triphosphate derivatives generated intracellularly
 Inhibits Inosine Monophosphate dehydrogenase (IMPDH), mRNA capping & viral RNA synthesis
 Viral resistance to ribavirin is rare.
Ribavirin
Pharmacokinetics
 Oral bioavailability of ribavirin is ~50%.
 Partly metabolized and eliminated in a multi exponential manner
 long term t½ is > 10 days
 Ribavirin combined with peginterferon for 6–12 months as 1st line treatment for HCV

33.  Drugs active against human immunodeficiency virus (HIV) which is a retrovirus
 Clinical efficacy monitored primarily by plasma HIV-RNA assays and CD4 lymphocyte count
Class: Anti-retrovirus drugs
HIV Virus
 HIV is a single stranded RNA retrovirus
 Reverse transcription of proviral DNA from viral RNA(normally RNA is transcript from DNA)
 With the help of a viral RNA-dependent DNA polymerase (reverse transcriptase)
 HIV primarily infection attack on is the CD4+ helper T lymphocyte, later macrophages and some other cell
 When population of CD4 cells declines markedly (<200 cells/µL)
 Cell mediated immunity (CMI) is lost and opportunistic infections resulting death of patient

35. CLASS DRUGS
Nucleoside reverse transcriptase inhibitors
(NRTIs)
Zidovudine, Didanosine, stavudine,
Lamivudine, Abacavir, Tenofovir
Nonnucleoside reverse transcriptase inhibitors
(NNRTIs) Nevirapine, Efavirenz, Delavirdine
Protease inhibitors
Ritonavir, Atazanavir, Indinavir,
Nelfinavir, Saquinavir, Lopinavir
Entry ( Fusion ) inhibitor Enfuvirtide
CCR5 receptor inhibitor Maraviroc
Integrase inhibitor Raltegravir
Classification of Anti-Retroviral Drugs

36.  The two established targets for anti-HIV drug attack are:
(a)HIV reverse transcriptase: Which transcripts HIV-RNA into proviral DNA.
(b)HIV protease: Which cleaves the large virus directed polyprotein into functional viral proteins.
 In addition, some newer targets being exploited are:
 Fusion of viral envelope with plasma membrane of CD4 cells through which HIVRNA enters the cell
 Chemokine coreceptor (CCR5) on host cells which provide anchorage for the surface proteins of the virus
 HIV-integrase: Viral enzyme which integrates the proviral DNA into host DNA
Drug Target:

37.  Pharmacokinetics:
Absorption: Rapid absorption, but bioavailability is ~65%
Distribution:
 Plasma protein binding is 30% and CSF level is ~50% of that in plasma
 It crosses placenta and is found in milk
Metabolism: hepatic glucuronidation.
Excretion: urine
A: Nucleoside reverse transcriptase inhibitors ( Zidovudine )
Zidovudine
phosphorylated
in the host cell
Zidovudine triphosphate
selectively inhibits viral
reverse transcriptase enzyme
Zidovudine thus
prevents infection of
new cells by HIV
but has no effect on
proviral DNA that has
already integrated into
the host chromosome
 The first anti-retrovirus (ARV) drug zidovudine ( thymidine analogue ) was available for use in 1987

38. Adverse effects:
 Common: Anaemia and neutropenia
 Dose related toxicity: Nausea, anorexia, abdominal pain, headache, insomnia and myalgia
 Long term toxicity: Myopathy, pigmentation of nails, lactic acidosis, hepatomegaly, convulsions
Uses:
 Zidovudine is one of the two optional NRTIs used by National AIDs control organization (NACo) its first line
triple drug ART regimen ( 2 NNRTIs + Zidovudine)
 Immune status is improved and opportunistic infections become less common
 Zidovudine also reduces neurological manifestations of AIDS and new Kaposi's lesions
 Effects are limited from a few months to a couple of years after which its stops

39.  These are the nucleoside unrelated compounds
 Directly bind to HIV reverse transcriptase to inhibit transcription
 No need for intracellular phosphorylation
 They are non-competitive inhibitors
 More potent than AZT on HIV-1
 Do not inhibit HIV-2, if used alone resistance is developed
 NNRTIs started to be approved in 1997
B: Non-nucleoside reverse transcriptase inhibitor (NNRTIs)
Ex- Nevirapine, Efavirenz, Delavird

40.  From large viral polyprotein ; aspartic protease enzyme pro structural proteins and enzymes (including reverse
transcriptase and integrase) of the virus in the infected cell.
 It acts at a late step in HIV replication, i.e. maturation of the new virus particles when the RNA genome
acquires the core proteins and enzymes.
 Retroviral protease inhibitors (PIs)Bind to the active sit of protease molecule interfere Cleaving
function(broken into various functional components)
 Prevent further rounds of infection.
 Uses:
 Viral resistance developed within months due to selection resistant mutants so Combination of NRTIs with PIs
is advised.
 Adverse effects:
 Gastrointestinal intolerance, asthenia, headache, dizziness, limb and facial tingling, numbness and rashes.
 Lipodystrophy (abdominal obesity, buffalo hump with wasting of limbs and face)
 Dyslipidaemia (raised triglycerides and cholesterol) and insulin resistance
 Indinavir crystalises in urine and increases risk of urinary calculi
C: Retroviral protease inhibitors (PIs)

41. 1) The binding of HIV surface protein gp120 to the
CD4 receptor.
2) A conformational change in gp120, which both
increases its affinity for a co-receptor and
exposes gp41
3) The binding of gp120 to a co-receptor either
CCR5 or CXCR4.
4) The penetration of the cell membrane by gp41
5) Which approximates the membrane of HIV-T cell
and promotes their fusion
6) The entry of the viral core into the cell
7) Entry inhibitors work by interfering with one
aspect of this process
Binding, fusion, entry sequence of retrovirus

42.  Active against HIV-1 but not active against HI Enfuvirtide (HIV-derived synthetic peptide)
 Binding to HIV-1 envelope transmembrane glycoprotein (gp41)
 This is responsible for fusion of viral and cellular membranes
 After binding prevention of fusion of the two membrane
 Which causes entry of the virus into the cell is blocked
 Problems associated with therapy is injections are painful and cause local nodules/cysts.
 The cost and inconvenience
D: Entry (fusion) inhibitor: Ex- Enfuvirtide, Enfuvirtide

43.  The HIV envelope contains globular glycoprotein gp120
 Will bind to cell membrane receptor i:e CCR5 chemokine receptor (most HIV are CCR5-tropic)
 Then attach to the CD4 site of host cell Maraviroc blocks
 Host cell CCR5 receptor
 Anti retroviral action
 It has no effect on HIV strains that are CXCR4 receptor tropic
 CXCR4 is an alternative chemokine receptor which also can bind gp 120, or dual CCR5/CXCR4 tropic
E: CCR5 receptor inhibitor (Maraviroc)

44. PHARMACOKINECTICS

45.  HIV-proviral DNA
 Transcripted in the cytoplasm of host cell
 Translocation to nucleus along with an integrase enzyme
 Raltegravir Block: Infection to host cell
 Uses: It is active against both HIV-1 and HIV-2
 Adverse Drug Reaction:
 nonspecific; myopathy is a potential toxicity.
 However, raltegravir is a new drug
 Efficacy and safety need to be established.
F: Integrase inhibitor ( Raltegravir )

47. Side Effects of Antiretroviral

48. References
• A review: Mechanism of action of antiviral drugs - PMC (nih.gov)
• Antiviral drug – Wikipedia
• KD TRIPATHI, Essentials of Medical Pharmacology, 6th edition
• Goodman & Gilman's The Pharmacological Basis of Therapeutics
• Pathogenesis and disease - Human Herpesviruses - NCBI Bookshelf (nih.gov)
• Viral Pathogenesis - Medical Microbiology - NCBI Bookshelf (nih.gov)

49. THANKYOU..!!