Anti-viral agents

 Virus
o Obligate intracellular parasite
o Virus replicates using host-cell machinery
o

Vaccines (Prophylactic) Anti-viral drugs

Live or inactive Difficult to develop
Given by governments/WHO Target group has varying
severities
Herd immunity or defined target
group
 Targets for anti-viral drugs
o Substrate analogues
 Competitive inhibitor
 Rational drug design
 When structure is known in depth
o Examples
 Acyclovir
 Modified nucleoside -- Similar shape to Guanosine
o Chain terminator
 Backs 3’ OH group
o Higher affinity for viral DNA
 Given in unphosphorylated form
o Viral Thymidine Kinase phosphorylates
 Resistance is rare
o Maps to the Thymidine Kinase
 Mutation in Thymidine Kinase is rare because it
reduces fitness
 Therefore HIGH BARRIER to mutation
 Influenza
o The features of a good antiviral against influenza
 Easy to administer
 Low side effects
 Effective against a range of influenza types
 Targets unique and essential gene or function of virus
o Examples in antivirals;
 Relenza and Tamiflu
 Both mimic Sialic acid, therefore bind to Neuraminidase and prevent
virus entry and exit
o Have a higher affinity to Neuraminidase than Sialic acid
o Virus becomes ‘stuck’
 Relenza
o Given as spray
 Tamiflu
o Tablet
o Trials
 Metanalysis by Cochrane
 Shortens illness
 4% of cases causes Nausea
 Retrospective analysis (based on real life outcome)
 Risk of death is halved if started within 4
hours of symptoms
 Adamantanes
 Cyclic amine
 Discovery
o By-product of petroleum refinement
o By testing random chemicals
 Acts on the M2 cell surface protein
o Amantane sits in the channel and blocks it
 Therefore virus locked in endosome, cannot enter
cell
o Allows protons to get into the core of the virus and acidify it
 There is resistance
o Single point mutation in M2
o Little cost to fitness
o Therefore drug becomes useless
o Examples of resistant strains
 Most H3N2
 Many H5N1
 Swine flu PH1N1
 Baloxavir
 Acts on RNA polymerase
 Patient gets better around 1 day sooner
o Kills virus in the nose and throat
 Resistance
o Single point mutation in PAI38I
o Common in children
 HIV
 Combination therapy used
 Slim chance that one genome acquires resistance to all
o Although
 HIV is lifelong therefore long time for resistance to
occur