The methyl ester of amphotericin B (AME) is water soluble, retains antifungal activity, and is significantly less toxic in mammals than amphotericin B. In contrast to amphotericin B, which is not water soluble, AME exhibits antiviral effects against vesicular stomatitis virus, herpes simplex virus types 1 and 2, Sindbis virus, and vaccinia virus in a plaque reduction assay. No antiviral effects could be demonstrated against the unenveloped adenovirus type 4 or echovirus type 11. The extent of virus inactivation was found to be dependent upon the AME concentration, contact time, and temperature. No consistent effect of the virus concentration on the probability of plaque-forming unit inactivation could be determined. The antiviral effects of AME were partially antagonized by the presence of serum. Binding of AME to vesicular stomatitis virus was demonstrated by the comigration of drug and virus in linear sucrose gradients. AME represents a new class of antiviral agents with activity at concentrations relevant to therapeutics. Sterol components of the host cell membrane that become incorporated into the viral envelope are postulated as the site of reaction with AME.Amphotericin B is a polyene macrolide antimicrobical agent that is currently the most effective agent available for the treatment of many systemic fungal infections in man. The biological properties of the polyenes result primarily from interaction with sterol components of the cell membrane (6). The major disadvantages of amphotericin B are its poor solubility in water, necessitating stabilization of suspensions with deoxycholate, and its numerous toxic side effects. In contrast, the methyl ester of amphotericin B (AME) is water soluble and less toxic and retains antifungal activity (3,8). Recently, activity of AME against herpesviruses has been reported (11). We describe the binding of AME to vesicular stomatitis virus (VSV), the kinetics of the antiviral action, and the spectrum of activity against several classes of enveloped and unenveloped viruses.
MATERLALS AND METHODSReagents. Cells were grown in Eagle basal medium with 10% fetal bovine serum (FBS). Maintenance medium consisted of Eagle basal medium with 2% FBS. Gentamicin (10 ug/ml) was added to all media. Hanks balanced salt solution with 0.5% gelatin, but no serum, was used for the dilution of viruses and AME.The hydrochloride of AME was kindly supplied, as a yellow, dry powder, by Carl P. Schaffner, The Waksman Institute of Microbiology, Rutgers University, New Brunswick, N.J. Tritiated AME had a specific activity of 1.2 x 106 dpm/mg. One-half-milliliter portions of a stock solution of AME in sterile distilled water (2 mg/ml) were frozen at -70°C; no turbidity or precipitation was observed.