[Effect of remantadine and amantadine on the interaction of influenza virus proteins with model lipid membranes]. / Vliianie remantadina i amatadina na vzaimodeistvie belkov virusa grippa s model'nymi lipidnymi membranami.

The influence of adamantane derivatives (remantadine and amantadine) on the surface charge of lipid bilayer when they are adsorbed on an artificially formed bilayer lipid membrane (BLM) was studied. The presence of the final number of binding centres on the BLM surface for remantadine and amantadine molecules and the cooperative nature of interaction of these compounds with the lipid bilayer were demonstrated. The features of interaction of influenza virus proteins isolated from the virion--M protein and a mixture of surface glycoproteins--were studied. Both antiviral compounds were shown to reduce markedly M protein adsorption on the lipid bilayer and to affect negligibly the sorption properties of the surface glycoproteins. Remantadine molecules interact directly with M protein molecules reducing their hydrophobic properties and, thereby, reducing the affinity of this viral polypeptide to lipid bilayer.

Interaction of influenza virus proteins with planar bilayer lipid membranes. I. Characterization of their adsorption and incorporation into lipid bilayers.

Alterations in the surface potential difference (delta U) of asolectin planar bilayer lipid membranes were measured following the adsorption of isolated matrix protein (M-protein) or neuraminidase of influenza virus. The method used was based upon measurement of the bilayer lipid membrane capacitance current second harmonic. The delta U dependence on the M-protein and neuraminidase concentration indicates different mechanisms of adsorption of these viral proteins by the lipid bilayer. The conductance (G0) dependence of the bilayer lipid membrane with different compositions on the concentration of isolated surface glycoproteins, hemagglutinin and neuraminidase, M-protein or neuraminidase was investigated. The change in G0 for M-protein was observed only after adsorption saturation had been achieved. Neuraminidase alone does not affect the membrane conductivity. The surface charge and lipid composition of the lipid bilayer influences the adsorption and incorporation of influenza virus M-protein and surface glycoproteins. The reversibility of protein incorporation into the bilayers was investigated by a perfusion technique. The results show reversibility of surface glycoprotein incorporation while M-protein binding appears to be irreversible.

Interaction of influenza virus proteins with planar bilayer lipid membranes. II. Effects of rimantadine and amantadine.

The dependence of the surface potential difference (delta U), transversal elasticity module (E1) and membrane conductivity (G0) on the concentrations of the antiviral drugs, rimantadine and amantadine was studied in the planar bilayer lipid membrane system. The method used was based on independent measurements of the second and third harmonics of the membrane capacitance current. The binding constants of bilayer lipid membranes obtained from the drug adsorption isotherms were 2.1 X 10(5) M-1 and 1.3 X 10(4) M-1 for rimantadine and amantadine, respectively. The changes in G0 took place only after drug adsorption saturation had been achieved. The influence of rimantadine and amantadine on the interaction of bilayer lipid membranes with matrix protein from influenza virus was also investigated. The presence of 70 micrograms/ml rimantadine in the bathing solution resulted in an increase in the concentration of M-protein at which the adsorption and conductance changes were observed. The effects of amantadine were similar to those of rimantadine but required a higher critical concentration of amantadine. The results obtained suggest that the antiviral properties of rimantadine and amantadine may be related to the interaction of these drugs with the cell membrane, which can affect virus penetration into the cell as well as maturation of the viral particle at the cell membrane.

[Changes in the electrical and visco-elastic properties of bilayer lipid membranes during interaction with proteins and lipoproteins]. / Izmenenie élektricheskikh i viazkouprugikh svoistv bisloinykh lipidnykh membran pri vzaimodeistvii s belkami i lipoproteidami.

A method for simultaneous registration of planar bilayer lipid membrane (BLM) DC conductance G, capacitance C, surface potential difference delta phi and transversal elasticity module E is developed. C, delta phi and E are proportional to the amplitude of the first, second and third harmonics of capacitance current respectively. A comparative study of the interaction of BLM with very low density lipoproteins (VLDL), influenza virus matrix protein (M-protein) and yeast invertase was carried out. The kinetics of delta phi, E and G changes at different concentrations of VLDL, and dependence of delta phi and G on M-protein and invertase concentration was investigated. It is shown for VLDL invertase and M-protein that the changes in delta phi and E occur before the change in G. The method used permits to study peculiarities of individual stages of interaction between charge particles, supramolecular structures and lipid membranes.