[Remantadine binding with influenza virus nucleoids in vitro and infected cells].

Interactions of the tritium-labeled antiviral preparation remantadine with nucleoids and ribonucleoprotein (RNP) of influenza virus were studied. The studies were carried out both in vivo, in infected cells, and in vitro upon direct contact of the preparation with subviral structures isolated from the infected cell and from virions. Autoradiography of the cells treated with 3H-remantadine showed its association with nuclei (possibly with nuclear membranes). The analysis of the results of gradient centrifugation showed remantadine to bind to virus nucleoids in vivo and in vitro without interacting directly with RNP. Polyacrylamide gel electrophoresis of viral proteins revealed association of remantadine with matrix M protein. Nucleoids isolated from a remantadine-resistant virus variant bound much less remantadine than those of a sensitive variant. Some suggestions on the kind of interaction leading to the formation of such stable associations are made. It is also suggested that remantadine prevents M-protein interaction with cell membranes (probably, with the nuclear membrane) thereby blocking further "uncoating". Because RNP is not released from the M-protein layer and does not penetrate into the nucleus, the nuclear stage of virus reproduction is shut down.