Antiviral activity of NMSO3 against respiratory syncytial virus infection in vitro and in vivo

NMSO3, a sulfated sialyl lipid was evaluated for its efficacy against respiratory syncytial virus (RSV) and other myxovirus infections in cell culture. The median effective concentration (50% effective concentration, EC50) of NMSO3 against replication of the Long strain of RSV in HEp-2 cells was 0.2 and 0.32 μM by optical ELISA and the plaque reduction method, respectively. On the other hand, the corresponding values for ribavirin were 10.5 and 11.2 μM, respectively. NMSO3 showed potent activity against other laboratory strains as well as fresh clinical isolates of RSV, and the average EC50 was similar to that for Long strain. NMSO3 exhibited minimal cytotoxicity against HEp-2, MDCK, HMV-2 and Vero cells for which the median cytotoxic concentration (CC50) was more than 685 μM. The selectivity index [SI=(CC50 for HEp-2/EC50)] of NMSO3 for RSV exceeded 2978 and that of ribavirin was 6. The EC50 of NMSO3 against influenza virus (FluV) A (H3N2) was 23.8 by the MTT method using HMV-2 cells, and 17.8 μM by the TCID50 method using MDCK cells. NMSO3 did not inhibit replication of influenza B virus, parainfluenza virus type 2 and canine distemper virus at 103 μM. NMSO3 inhibited RSV infection of HEp-2 cells when it was added between 0 and 1.5 h after virus infection. By a temperature shift experiment during the period of contact between the virus and cells, NMSO3 inhibited both the binding of RSV to the cells and its penetration into the cells. Prophylactic and therapeutic efficacy of NMSO3 against RSV infection in cotton rats was examined. Intraperitoneal administration of 100 mg/kg per day of NMSO3 to cotton rats from 1 day before or 1 h after to 3 days after the RSV infection, once a day every day, decreased the RSV titer in lungs to 10−1.26 to 10−1.63 compared to the control rats which were infected with RSV and left untreated.