Studies with a hydrophobic, spin-labeled virucidal agent.
A spin-labeled virucidal agent was synthesized, purified, and tested for its activity against the enveloped bacterial virus phi6 and herpes simplex virus. This compound, designated BPN, inactivated greater than 99% of phi6 and herpes simplex virus in vitro at concentrations as low as 0.1 mM. Detailed studies were carried out on the mechanism of inactivation of phi6 by BPN. These studies revealed that treatment of phi6 by BPN specifically removes a single envelope protein that is considered to be responsible for adsorption of the virus to the host cell. Related experiments with the phi6 host, Pseudomonas phaseolicola strain HB10Y, showed that this organism is insensitive to the effects of BPN. The basis for the differential sensitivity of phi6 to BPN, in comparison to the host cell, was investigated by electron spin resonance techniques. It was found that, for phi6, HB10Y, and their extracted phospholipids, BPN is localized in the hydrocarbon zones of the membrane bilayer. However, in the case of phi6, the rotational mobility of BPN is much reduced in comparison to that in HB10Y and the phospholipid preparations. Furthermore, an Arrhenius plot of rotational correlation time (tau(c)) showed a marked discontinuity in slope at 31 degrees C in the case of phi6, but not for the other samples studied. This suggests a strong interaction between the phi6 envelope proteins and the lipid domains in which BPN is localized. Calculations based on the known lipid and protein composition of phi6 indicate that there is an absence of "free-lipid" pools in the viral envelope. It is suggested that BPN localizes in free-lipid pools of cell membranes, where its presence is of little or no consequence, but that in phi6 the BPN perturbs the hydrophobic interactions between phospholipids and proteins in the envelope.
D000998:Antiviral Agents / Q000032:analysis* / Q000138:chemical synthesis / Q000494:pharmacology; D001435:Bacteriophages / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000032:analysis* / Q000138:chemical synthesis / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004591:Electrophoresis, Polyacrylamide Gel; D010080:Oxazoles / Q000032:analysis* / Q000138:chemical synthesis / Q000494:pharmacology; D011549:Pseudomonas / Q000187:drug effects; D013113:Spin Labels / Q000138:chemical synthesis*
D000998:Antiviral Agents; D003497:Cyclic N-Oxides; D010080:Oxazoles; D013113:Spin Labels