Point M2 mutant viruses yield in different concentrations of amantadine: Closed squre -M2V27T; open square- M2A30P; closed circle- M2S31N; open triangle , M2del29-31; closed triangle , wild type.

 

**Wild-type virus yield was very low as compared to all mutants overall. Plaque size (not shown) yielded the same results. All the mutants showed resistance to amantidine.

**At 0.5 micrometers there was really no marked change in the amount of virus that was produced in the mutant viruses. For the wild-type virus at this same concentration, the drug decreased the virus yield by 60% at low concentrations and even further at 5 micrometers.

**At 5 micrometers the replication of the M2 mutant viruses was either not affected or inhibited only slightly. The biggest change was when 50 micrometers of amantidine was used. M2 mutant viruses showed the biggest decrease at this concentration. Wild-type virus did not change in the amount of virus that was yielded.

**All M2 mutants were more resistant to amantadine than the wild-type virus.

Why such a difference between wild-type and mutants? Specific inhibition and non-specific action of the drug.

  Specific inhibition At concentrations lower than 50 micrometers, the drug selectively inhibits viral replication for influenza A.

Non specific inhibition At concentrations higher than 50 micrometers, there is an increase in pH of endosomes which then inhibits the HA membrane fusion activity in endocytosis.