• nucleoside analog of guanosine 
• 50x higher activity against CMV 
• Needs a virally encoded phosphorylating agent, found in CMV infected cells to become an active monophosphate 
• Valganciclovir is the L-valyl ester prodrug of ganciclovir 
• Neutropenia and thrombocytopenia are side effects 
• similar to acyclovir but has an additional hydroxymethyl group on acyclic side chain

• Cytidine nucleoside analogue for herpesviruses 
• metabolized to its active diphosphate form by cellular enzymes 
• diphosphate active form actes as both a competitive inhibitor w.r.t dCTP and as an alternative substrate for viral DNA polymerase
• Resistance in CMV is due to mutations in viral DNA polymerase 
• excreted mainly through the kidneys 
• nephrotoxic
• only used against CMV in case of failure of other drugs

• nucleotide analogue
• inhibitor of RNA synthesis
• needs to be phophorylated to become active
• mechanism incompletely understood:
• alters cellular nucleotide pool
• inhibits viral mRNA synthesis
• intracellular phosphorylation into mono-,di-,and triphophate derivatives by host cell enzymes
• monophosphate: competitvely inhibits cellular inosine 5' phophate dehydrogenase and interferes with synthesis of GTP
• triphosphate: competitively inhibits GTP-dependent 5' capping of viral mRNA, inhibits RNA polymerase
• for treatment of HCV in combination with interferon
• aerosol for RSV infection in children 

• Hydrophobic amines (weak organic bases) inhibit the ion channel function of the M2 protein of influenza A viruses
• By blocking proton permeation and prevent M2-mediated changes in pH
• inhibition of the acid-mediated dissociation of the matrix protein from the ribonucleoprotein complex within endosomes early in replication
• Inhibits several steps in early replication
• Only oral preparations
• Amantadine excreted by the kidney without metabolism
• Rimantadine: metabolized through the liver

• Neuraminidase inhibitor
• Oral oseltamivir is effective in the treatment and prevention of influenza A and B virus infections.
• reduces illness duration by about 1 to 2 days
• reduces the risk of complications leading to antibiotic use by 40% to 50%
• Treatment is associated with approximate halving of the risk of subsequent hospitalization in adults
• When used for prophylaxis during the influenza season, oseltamivir (75 mg once daily) is effective (approximately 70% to 90%) in reducing the likelihood of influenza illness in both unimmunized working adults and in immunized nursing home residents
• short-term use (7 to 10 days) protects against influenza in household contacts

• Guanosine analog
• 3-carbon acylic carbon instead of cyclic ribose
• Needs to be phophorylated by thimidine kinase to be active.
• Phosphorylation occurs only in cells infected by
• certain herpes viruses that induce the thymidine kinase
• 100th fold greater affinity of acyclovir to viral DNA polymerase than for cellular DNA polymerase
• Inhibits viral DNA polymerase and terminates viral DNA chain growth.
• Does not eliminate the virus from the host
• Formulations:
• Oral
• Topical
• Parenteral
• Used for Herpes Simplex Virus type 1 and 2 as well as Varicella Zoster Virus
• Valacyclovir is a prodrug of acyclovir that is better absorbed

• IFN-α and IFN-β exhibit antiviral and antiproliferative actions:
• stimulate cytotoxic activity of lymphocytes, NK cells, and macrophages
• up-regulate MHC I  and other surface markers
• IFNγ- less antiviral activity but more potent immunoregulatory effects:
• macrophage activation
• expression of MHC II  
• mediation of local inflammatory responses
• The binding of IFN to specific cell surface receptor molecules signals the cell to produce a series of antiviral proteins
• Clinical use: Only IV
• Attachment of IFN proteins to large, inert polyethylene glycol(PEG) molecules (pegylation):
• slows absorption
• decreases clearance
• provides higher and more prolonged serum concentrations
• enable once-weekly dosing
• IFN α: Used in treatment of HCV, HBV, Kaposi sarcoma, cancer (ex. Lymphoma)
• IFN β: Multiple sclerosis

• Entry inhibitors
• Nucleoside and nucleotide reverse transcriptase inhibitors
• Non-nucleoside reverse transcriptase inhibitors
• Integrase inhibitors
• HIV protease inhibitors

• anti retroviral
• Inhibits penetration and unoating
• Inhibits the action of the viral fusion protein gp41, stops conformational change

• anti retroviral
• Inhibits penetration and uncoating
• Inhibits CCR5 coreceptor

Nuleotide and nucleoside reverse transcriptase inhibitors

NRTI

• anti retroviral
• Like all nucleoside analogs, they need to be phosphorylated to be integraed in the growing chain

• anti retroviral
• bind to a hydrophobic pocket in the p66 subunit of the HIV-1 reverse transcriptase
• These compounds induce a conformational change in the 3-D structure of the enzyme that greatly reduces its activity
• act as noncompetitive inhibitors

• anti retroviral
• integrase inhibitor
• inhibits the catalytic activity of integrase, preventing integration of the proviral gene into human DNA

• anti retroviral
• peptide like chemicals that competitively inhibit the action of the virus protease that cleaves polyproteins into structural proteins

• Inhibits DNA polymerase
• CMV, HSV, VZV

• Lamivudine, adefovir, entecavir,
• Tenofovir
• Interferon