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LECTURE 19:
Anti-viral drugs
Waqas Nasir Chaudhry
Viro100:
Virology
3 Credit hours
NUST Centre of Virology & Immunology
Anti-viral drugs
• For a long time there were very few anti-viral
drugs available for clinical use compared with
the number of anti-bacterial and anti-fungal
drugs.
• This was because it was difficult to find
compounds that interfere specifically with
viral activities without causing significant
harm to host cell activities.
Virus activities that are potential drug targets. A generalized view of virus replication
is depicted.DNA replication provides a target if the virus produces enzymes (e.g. DNA
polymerase, thymidine kinase) distinct from those of the host.
Development of anti-viral
drugs
1. Screening compounds for anti-viral activity
2. Rational design of anti-viral drugs
1- Screening compounds for anti-viral
activity
• In this approach to the search for clinically useful
anti-viral drugs, large numbers of compounds are
tested for possible anti-viral activity.
• The screening procedure involves testing
dilutions of the compounds against a range of
viruses growing in cell cultures.
• Evidence that a compound interferes with the
replication of a virus might include inhibition of
cytopathic effect (CPE) or of plaque formation.
• For each potentially useful compound the
concentration that inhibits CPE or plaque
formation by 50 percent is determined.
• This concentration of the drug is known as the
50 percent inhibitory concentration (IC50).
• For example
– Peramivir IC50 1.1 ± 0.02 nM
– Oseltamivir IC50 0.21 ± 0.01 nM
• Potent influenza virus sialidase inhibitors
2- Rational design of anti-viral drugs
• Screening compounds for anti-viral activity
has been largely replaced by the rational
design of drugs
• The process of designing an anti-viral drug
starts with deciding upon a target activity for
the drug
• Once this has been selected, it is necessary to
choose a target protein, such as a viral
enzyme, that is involved in that activity.
• A detailed picture of the three dimensional
structure of the protein is derived using
techniques such as X-ray crystallography and a
target site in the protein is selected.
• Computer programs are then used to design
compounds that will bind to the target site
with the aim of inhibiting the activity of the
virus protein.
Safety of anti-viral drugs
• If a compound is to have clinical value it must
not only inhibit virus replication, but it must
cause little or no harm to the host.
• The research and development procedures
therefore include incubating uninfected cell
cultures with the compound and examining
them for damage such as death or inhibition
of cell division.
• The potential value of a compound can be
assessed by determining the ratio of its cell
toxicity to its anti-viral activity.
• This ratio is known as the selectivity index (SI)
and is expressed by the formula
• A compound with a low IC50 and a high SI is
most likely to have value as an anti-viral drug.