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General background
Structure of viruses
Categories of viruses: DNA and RNA-based
Examples of viral diseases
General anti-viral approaches
(anti-viral drugs):
“amantadine”; “interferon”; “acyclovir”; “azt”; “indinavir”; etc.
General principles
Viruses are parasitic, i.e. they utilize:
Host metabolic enzymes
Host ribosome for protein synthesis
Structure of viruses
Nucleic acid core: DNA or RNA
Often contain crucial virus-specific enzymes
Surrounded by protein: “capsid”
… and sometimes an outer lipid “envelope”
Complete viral particle: “virion”
Often visible by electron microscopy:
Paramecium bursaria
http://www.cgl.ucsf.edu/Research/virus/capsids/viruses.html chlorellavirus (infects green algae)
General principles: DNA viruses
Overview
Drug approaches that target the uncoating of the influenza viral particle
Amantadine HCl
Rimantidine HCl
Interferon:
Signal-transducing proteins that interfere with viral protein expression
Example 1: Targeting early stages of viral infection
Amantadine HCl
Rimantadine HCl
Interferon
What is interferon?
Discovered in 1957
Proteins produced naturally by cells in immune system after exposure to
viruses
May be a “natural anti-viral factor”
Pharmaceutical use:
Not practical as a pharmaceutical until
mass recombinant production (~1980s)
Still considered a “drug of the future”
Example 1: Targeting early stages of viral infection
(RNA viruses):
influenza; chronic hepatitis; common cold
(also):
breast cancer; lung cancer;
Karposi’s sarcoma (cancer associated with AIDS)
Pharmacokinetics:
Not orally bioavailable
Typically routes: intramuscular, subcutaneous, topical (nasal spray)
Example 1: Targeting early stages of viral infection
Acyclovir
A drug primarily used to treat herpes infections (HSV-1, HSV-2)
This can be thought of as a purine mimic!
Note similarity to 2’-deoxyguanosine: lack of 3’-hydroxyl (!!)
Acyclovir: Pharmacokinetics
Fairly poor oral absorption (15-30%)
Improved by design of suitable prodrugs:
Example 2: Specifically Targeting DNA viruses (HSV)
Idoxuridine
Also used to treat herpes infections (HSV-1, HSV-2, VZV)
This is a pyrimidine nucleoside mimic!
Note similarity to 2-deoxythymidine: with interesting iodouridine base
Example 2: Specifically Targeting DNA viruses (HSV)