Multiple Actions of Amantadine Against Influenza Viruses

Low pH-induced pore formation by spike proteins of enveloped viruses

“…Second, the role of the anti-influenza virus drug amantadine (acting on the M2 protein) early in infection is so far not fully understood. Some strains such as the Rostock strain are particularly sensitive to amantadine late during the infectious cycle but remain relatively insensitive at early stages (Hay & Zambon, 1984). One possible explanation for these findings could be that other virus proteins, e.g.…”

Entry and uncoating of enveloped viruses

“…Susceptibility to the drug is retained if the drug is added shortly after infection (Hay and Zambon, 1984). Hence, in addition to its early effect in virus uncoating (see below), M2 is thought to have an important function in the assembly of influenza virus.…”

“…Some strains, e.g. the Rostock strain, are particularly sensitive to amantadine late during the infectious cycle but remain relatively insensitive at the early stage (Hay and Zambon, 1984 (Garoff et al, 1980a). The spikes are arranged on a T 4 lattice (von Bonsdorff and Harrison, 1978;Adrian et al, 1984;Vogel et al, 1986;Choi et al, 1991).…”

Influenza A Virus M2Ion Channel Activity Is Essential for Efficient Replication in Tissue Culture

“…Analyses of the effect of amantadine on influenza A virus replication in tissue culture indicated that influenza virus is sensitive to the drug but that the sensitivity of virus growth depends somewhat on the strain of influenza A virus (50% inhibitory concentration, ϳ1 to 10 M amantadine) (1,16,57). At optimal drug concentrations, virus yield was found to be inhibited 90 to 99% depending on the subtype tested.…”

“…At optimal drug concentrations, virus yield was found to be inhibited 90 to 99% depending on the subtype tested. However, it is quite clear from the early studies, provided amantadine was added to cells either before infection or at the time of infection, that although virus binding and virus penetration occurred, there was no detectable primary transcription of the input genome by the virion-associated RNA transcriptase (16,25,57). Thus, the finding that influenza A viruses that lack an M 2 ion channel activity grow normally in tissue culture (68) is seemingly inconsistent with the effect of amantadine on virus replication in tissue culture.…”