Chapter 9

Smallest of all self-replicating

organisms
The simplest viruses contain a small
amount of DNA or RNA surrounded by
an uncomplicated protein coat.
Obligate cellular parasites composed
of a NA core surrounded by a
proteinaceous outer shell

The virus turns the biochemical
systems of the host cell to its own
purposes, completely subverting the
infected cell.
An adult virus possesses only one
type of NA (either DNA or RNA)

1. Nucleic acid content
2. Viral morphology
3. Site of replication in cell
4. Coating
5. Serological typing
6. Cell types infected
1. Adsorption
2. Entry
3. Uncoating
4. Transcription
5. Translation
6. Assembly
7. Release
Vaccines are used to prevent most
viral diseases
Polio, rubella, measles, mumps, influenza,
yellow fever, encephalitis, rabies, smallpox
and hepatitis B
Must be sufficiently antigenic to induce
an effective antibody response
Must not cause the disease it is
designated to prevent

alternative to active immunization for
the prevention of viral infection
interferes with a step in early viral
infectivity
Attachment of the virion to the host cell
Entry into the cell
Release of the viral nuclein acid from the
protein coat
Ex. Adamantanamines (Amantadine &
Rimantadine)
Amantadine (Symmetrel)
1-adamantanamine hydrochloride
Rimantadine (Flumadine)
a-methyl-1-adamantane methylamine hydrochloride
unusual caged tricyclic amines with the
following structure:
MOA:
they inhibit an early step in viral replication,
most likely viral uncoating
in some strains they affect a later step that
probably involves viral assembly, possibly by
interferring with hemagglutinin processing
for prevention and treatment of
influenza A virus infections
Amantadine also used for parkinsons

potent cytokines - antiviral,
immunomodulating, and
antiproliferative
synthesized by infected cells - elicit
either an antiviral state in neighboring
cells or a natural killer cell response
that destroys the initially infected cell
Inhibits:
Viral penetration or uncoating
Synthesis of mRNA
Translation of viral proteins
Viral assembly and release
A. Inhibitors of DNA polymerase
1. Idoxuridine,USP (Stoxil, Herplex)
5-iodo-2-deoxyuridine
introduced in 1963 for the treatment of
herpes simplex keratitis.

A. Inhibitors of DNA polymerase
2. Trifluridine, USP
3. Vidarabine, USP
4. Acyclovir, USP
5. Valacyclovir Hydrochloride
6. Ganciclovir
7. Famciclovir and Penciclovir
8. Cidofovir
9. Foscarnet Sodium


B. Reverse Transcriptase
Inhibitors
an early event in the replication of HIV-1
is reverse transcription, whereby
genomic RNA from the virus is converted
into a cDNA-RNA complex; then into
double-stranded DNA ready for
integration into the host chromosome.
B. Reverse Transcriptase
Inhibitors
1. Zidovudine, USP (AZT)
3-azido-3-deoxythymidine
is recommended for the management
of adult patients with symptomatic
HIV infection(AIDS or ARC) who have
a history of confirmed Pneumocystis
carinii pneumonia.
B. Reverse Transcriptase
Inhibitors
2. Didanosine (ddI)
3. Zalcitabine, USP (ddCyd)
4. Stavudine (D4T)
5. Lamivudine (3TC)
C. Miscellaneous Nucleoside
Antimetabolites
Ribavirin, USP
1-B-D-ribofuranosyl-1,2,4-thiazole-3-
carboxamide
treatment for severe LRIs caused by
respiratory synctial virus (RSV)

A. Nonnucleoside reverse
transcriptase Inhibitors(NNRTIs)
represent several structurally
distinct classes.
share a number of common
biochemical and pharmacological
properties.
1. Nevirapine (Viramune)
more than 90% absorbed by the oral route
and widely distributed
distributed well into breast milk and
crosses placenta
2. Delavirdine (Rescriptor)
Must be used with at least 2 additional
antiretroviral agents
3. Efavirenz (Sustiva)
also mandated for use with at least 2 other
antiretroviral agents
B. HIV Protease Inhibitors
designed to mimic the transition state
of hydrolysis at the active site
these compounds are called
Analogue inhibitors
Cause dyslipidemia (inc. cholesterol
and triglycerides), protease paunch
buffalo hump, facial atrophy, breast
enlargement
1. Saquinavir (invirase)
well tolerated following oral administration
Poor absorption but increased with fatty meal
2. Indinavir (Crixivan)
with high fat diet, achieves a maximum serum
concentration of 77% of the dose
3. Ritonavir, Amprenavir, and Nelfinavir
have similar properties and cautionary
statements
cause dyslipidemia; and inhibit CYP 3A4.

C. HIV Entry Inhibitors
entry of HIV into a cell is complex
process that involves several
specific membrane protein
interactions
D. Chemokine Receptor Binders
most HIV-1 isolates rely on the
CCR5 coreceptor for entry(R5
strains).
E. Inhibitors of gp41 Fusion Activity
The Fusion of the HIV-1 viral envelope
with host plasma membrane is mediated
by gp41, a transmembrane subunit of
HIV-1 glycoprotein subunit is complex
F. Integrase (IN) Inhibitors
two closely related types of small
molecules that block strand transfer
catalyzed by recombinant integrase
have been identified