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 phi 6 and herpes simplex virus. This compound, designated BPN, inactivated greater than 99% of phi 6 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 phi 6 by BPN. These studies revealed that treatment of phi 6 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 phi 6 host, Pseudomonas phaseolicola strain HB10Y, showed that this organism is insensitive to the effects of BPN. The basis for the differential sensitivity of phi 6 to BPN, in comparison to the host cell, was investigated by electron spin resonance techniques. It was found that, for phi 6, HB10Y, and their extracted phospholipids, BPN is localized in the hydrocarbon zones of the membrane bilayer. However, in the case of phi 6, 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/sub c/) showed a marked discontinuity in slope at 31/sup 0/C in the case of phi 6, but not for the other samples studied. This suggests a strong interaction between the phi 6 envelope proteins and the lipid domains in which BPN is localized. Calculations based on the known lipid and protein composition of phi 6 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 phi 6 the BPN perturbs the hydrophobic interactions between phospholipids and proteins in the envelope.
- Research Organization:
- Pennsylvania State Univ., University Park, PA (United States)
- OSTI ID:
- 5707855
- Journal Information:
- Antimicrob. Agents Chemother.; (United States), Vol. 17:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBIOTICS
PHARMACOLOGY
HERPES SIMPLEX
SENSITIVITY
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
BIOLOGICAL PATHWAYS
CELL MEMBRANES
DOSE-RESPONSE RELATIONSHIPS
DYNAMIC FUNCTION STUDIES
ELECTRON SPIN RESONANCE
HOST
IN VITRO
ANTI-INFECTIVE AGENTS
CELL CONSTITUENTS
DISEASES
DRUGS
INFECTIOUS DISEASES
KINETICS
MAGNETIC RESONANCE
MEMBRANES
REACTION KINETICS
RESONANCE
SKIN DISEASES
VIRAL DISEASES
550700* - Microbiology
550600 - Medicine
550200 - Biochemistry