ANIDINO-2,4-DIDEOXY-2,3-DEHYDRO-N-ACETYLNEURAMINIC ACID IS A HIGHLY EFFECTIVE INHIBITOR BOTH OF THE SIALIDASE (NEURAMINIDASE) AND OF GROWTHOF A WIDE-RANGE OF INFLUENZA-A AND INFLUENZA-B VIRUSES IN-VITRO

The sialidase (neuraminidase) inhibitor anidino-2,4-dideoxy-2,3-dehydr o-N-acetylneuraminic acid (4-guanidino-Neu5Ac2en) has been examined fo r the ability to inhibit the growth of a wide range of influenza A and B viruses in vitro in comparison with amantadine, rimantadine, and ri bavirin. 4-Guanidino-Neu5Ac2en inhibited plaque formation by laborator y-passaged strains of influenza A and B viruses, with 50% inhibitory c oncentrations ranging from 0.005 to 0.014 muM. A wider range of values (0.02 to 16 muM) was obtained with more recent clinical isolates, but in all cases 4-guanidino-Neu5Ac2en inhibited influenza A and B virus replication at lower concentrations than amantadine, rimantadine, or r ibavirin. Inhibition by 4-guanidino-Neu5Ac2en was not obviously affect ed by the passage history of the viruses or by resistance to amantadin e or rimantadine. 4-Guanidino-Neu5Ac2en was a very potent inhibitor of the sialidases of all the influenza viruses examined, with 50% inhibi tory concentrations ranging from 0.00064 to 0.0079 muM. No cytotoxicit y was observed with 4-guanidino-Neu5Ac2en at up to 10 mM. 4-Guanidino- Neu5Ac2en therefore represents a new potent and selective inhibitor of influenza A and B virus sialidase activity and replication in vitro.