STUDIES ON THE ANTIVIRAL ACTIVITY OF AMANTADINE HYDROCHLORIDE *

Tissue culture techniques. HeLa cells were infected with strains of parainfluenza viruses, types 2 (Greer) or 3 (C 243), obtained from R. M. Chanock, National Institutes of Health, Bethesda, Md. The LLC-MK2 line of monkey kidney cells6 was used for parainfluenza 3 and the WM strain of rubella v i r u ~ e s . ~ Other studies with rubella virus involved the chronically infected line previously described.8 The Long strain of respiratory syncytial virus, obtained from the American Type Culture Collection and grown in the H-L line of human epithelial cells, and the Japan 305 strain of influenza virus grown in primary calf kidney cells, were also used. Virus was detected by hemagglutination of guinea pig erythrocytes, by titration of infectivity, or by cytopathogcnic effect, depending on the particular cell-virus system. Antiviral activity was evaluated either by comparison of virus yield from treated and control cultures when measured by relative cytopathology, hemagglutination, or infectivity titrations, or by calculation of a therapeutic index? In vivo techniques. Swiss Webster mice or yearling ferrets were infected with influenza virus by a 30-minute exposure to aerosols of diluted suspensions of infected mouse lungs. The WR strain of vaccinia virus was given to mice intranasally. Disease was evaluated either by lung lesion scores10 or by mean survival times.' X-ray was given as previously described.11