Viral life cycle

1. Attachment
2. Fusion & Entry
3. Uncoating
4. Replication
5. Translation
6. Assembly
7. Release

Class Clinical use MoA pK Adverse effects

Antiherpesvirus
Acyclovir • Herpes simplex • Route of administration: iv, • ADR:
(Guanine • Herpes zoster oral, topical. • Well tolerated
nucleoside • Chickenpox • Distribution: widely, • Toxic effect may occur in
analogue) • Epstain-Barr virus including CSF. patients with renal failure.
• Excretion: by glomerular
filtration and tubular
secretion.

Acyclic purine nucleoside analogue 

competitive inhibitor of viral DNA
polymerase

Does acyclovir affect non-infected host

cells and Why?

Ganciclovir • >> activity against CMV. • activated through conversion to the

(acyclovir • treatment of CMV retinitis: nucleoside triphosphate (viral &
analogue) immunocompromised & cellular enzymes)
 transplant patients • inhibits viral DNA polymerase 
incorporated into DNA (chain
termination)

Viral hepatitis • no specific hepatitis A treatment (self-limiting: several weeks/ months)

• acute HAV  avoid alcohol & hepatotoxic medications
• Acute hepatitis B infection ( x antiviral drug treatment) Treatment: aggressive "fulminant hepatitis" / immunocompromised
• Antiviral drug (chronic virus hepatitis)  slow down liver damage, prevent complications (cirrhosis & liver cancer)

Hepatitis B
• Alpha interferon
• Pegylated alpha interferon
• Lamivudine
New generation
• Adefovir
• Entecavir
Hepatitis C
• Alpha interferon
• Pegylated alpha interferon
• Ribavirin
New generation
• NS3/NS4A protease inhibitors
• NS5B polymerase inhibitors
• NS5A replication complex inhibitors

IFN alpha • Chronic viral hepatitis B, C • Binds to specific cellular receptors • Administration: • Flu-like symptoms (fever, chills,
• Herpes virus infection • Activates signal-transduction subcutaneously, IM, topically. headache, fatigue) (~ hours after
• Influenza pathway  promotes synthesis of • Effects: administration)
• Cancer several proteins that inhibit: o Antiviral activity • CNS: mood disorders, depression,
o Kidney cancer o Entry o Antiproliferative activity confusion, seizures.
o Malignant melanoma o Uncoating o Immunomodulatory • Bone marrow supression
o Lymphomas o Replication activity (neutropenia)
o Leukemia o Translation • Liver toxicity (elevation of hepatic
• AIDS-related Kaposi’s o Assembly enzymes).
sarcoma. o Release • Mild hair loss.
• Miscarriage & birth defects.

Pegylated IFN Pegylated interferons (modified IFN): attachment molecule of polyethylen glycol
• Additon of polyethylen glycol improves pharmacokinetic properties + increases its clinical efficacy
o "masks" IFN from host's immune system  protects from breakdown;
o prolongs its circulation  increases T1/2.
o used once a week

Lamivudine • Chronic hepatitis B Inhibits both: • Prodrug: cellular enzymes • Well tolerated
Cytidine • High resistance (long-term • reverse transcriptase convert  triphosphate. • Neutropenia (high dose)
nucleoside therapy)  no longer • DNA polymerase. • High oral bioavailability • Redistribution/accumulation of
analogue recommended in current • Widely distributed in to the body fat (cushingoid appearance)
hepatitis B guidelines. tissues.
• HIV

Adefovir dipivoxil • Chronic hepatitis B • Entry → de-esterification to adefovir → • asthenia (weakness)

Adenosine • lamivudine-resistant HBV + conversion by cellular kinases (adefovir • renal tubular dysfunction (dose-
monophosphate compromised liver function diphosphate): competitive inhibitor of related)
nucleotide viral DNA polymerase & reverse • hepatotoxic  high doses
analogue transcriptase. (transaminase elevation)
• Hepatitis B DNA polymerase (higher • pregnancy Category C
affinity) for adefovir diphosphate >> • genotoxic
other cellular enzymes.

Entecavir Chronic hepatitis B • selectively blocks HBV polymerase • Food decreases absorption • development of resistance to HIV
Guanosine o 300-1300-fold higher affinity for by ~20% reverse transcriptase inhibitors in
nucleoside HBV vs human DNA polymerase • Intracellular half-life: 15 hrs HIV positive patients
analogue • >> potent (lamivudine, adefovir & • Renal elimination (filtered & • Pregnancy Category C
effective against lamivudine-resistant secreted)
HBV mutants

Ribavirin Hepatitis-C virus infection Converted intracellularly to a 5'- • Sudden deterioration of

Triazin riboside triphosphate derivative  inhibits viral respiratory function (infants)
analogue RNA polymerase & capping of viral mRNA • hemolytic anemia, cough, pruritus
at the 5' position and rash
• teratogenicity and embryotoxicity
o PREGNANCY CATEGORY X:
Ribavirin + Interferon is
absolutely contraindicated in
pregnancy and in male
partners of women who are
pregnant.

Grazoprevir Hepatitis-C virus infection • The viral NS3/NS4A serine protease (crucial for processing single polyprotein encoded by HCV RNA) into
Paritaprevir individually active proteins.
Glecaprevir • Without these serine proteins  RNA replication x occur  HCV life cycle is disrupted

NS3/NS4A
protease
inhibitors
Sofosbuvir Hepatitis-C virus infection • RNA polymerase (HCV replication)
NS5B polymerase Sofosbuvir (compete for the • processed with other HCV proteins into an individual polypeptide by the viral NS3/NS4A serine protease.
inhibitors enzyme active site)
Dasabuvir (target allosteric sites)

Ledipasvir • NS5A: essential for HCV RNA replication and assembly.

Elbasvir • formation of a membranous web along with viral protein NS4B  platform for replication.
Pibrentasvir
Daclatasvir
NS5A replication
complex
inhibitors
Anti-influenza
Amantadine • Prophylaxis + treatment of • Prevents viral uncoating  inhibition • Administration: • CNS: confusion, insomnia,
influenza A of viral M2 proteins (ion channels) orally dizziness.
• Inhibits viral assembly • Embryotoxic and teratogenic
effects (in rats)

Oseltamivir • Prophylaxis + treatment of • inhibitor of viral neuraminidase (NA)  • Route of administration: Tolerated better than amantadine
Sialic acid both influenza A and B inside influenza viral envelope. oral.
analogue • NA cleaves the connection between viral
hemagglutinin (HA) & glycoproteins on
the host cell surface.
 • Antiviral drug resistance is defined as a reduced susceptibility of virus to an antiviral drugs.

• Antiviral drug resistance is determined by specific mutations in the viral genome, which leads to alterations in the viral target point (HIV reverse transcriptase, herpes
simplex thymidine kinase).

• Viruses commonly associated with antiviral drug resistance:

• HIV

• Influenza virus

• Herpes virus

• Hepatitis B and C viruses

• To overcome antiviral drug resistance:

Combined antiviral therapy.

Viral Target Antiviral drug

replication
cycle
Fusion with Attachment CCR5-antagonist (e.g., maraviroc)
host cell
Penetration Fusion inhibitor (e.g., enfuvirtide)
Uncoating Release of nucleic acid Amantadine
Replication Reverse transcription NRTI (e.g., lamivudine)
of viral
NNRTI (e.g., nevirapine, efavirenz)
genome
DNA integration (integrase) Integrase inhibitors (e.g., dolutegravir, elvitegravir, raltegravir)

Nucleic acid synthesis (DNA Guanosine analogs (e.g., acyclovir, ganciclovir)

polymerase) Viral DNA polymerase inhibitors (e.g., cidofovir, foscarnet)

Guanine nucleotide synthesis inhibitor (e.g., ribavirin)

Protein Protein Interferon alpha
synthesis and
synthesis (transcription and tran
 assembly of slation)
viral
Proteolytic processing (protease) Protease inhibitors (e.g., atazanavir, darunavir, indinavir for HIV, bocepr
components
evir for HCV)
Release of Viral budding Neuraminidase inhibitors (e.g., oseltamivir, zanamivir)
new viruses fr
om host cell