The cyanobacterial lectin scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus

•The cyanobacterial lectin scytovirin inhibits the replication of Zaire Ebola virus and Marburg virus in vitro.•Scytovirin binds to the mucin domain of the Ebola virus glycoprotein.•The compound caused no detectable toxicity in cell culture assays or in mice.•Treatment of mice beginning the day before, the day of or the day after ZEBOV challenge resulted in 70–90% survival.•The short persistence of scytovirin in the serum necessitated s.c. dosing every 6h. The cyanobacterial lectin scytovirin (SVN) binds with high affinity to mannose-rich oligosaccharides on the envelope glycoprotein (GP) of a number of viruses, blocking entry into target cells. In this study, we assessed the ability of SVN to bind to the envelope GP of Zaire Ebola virus (ZEBOV) and inhibit its replication. SVN interacted specifically with the protein’s mucin-rich domain. In cell culture, it inhibited ZEBOV replication with a 50% virus-inhibitory concentration (EC50) of 50nM, and was also active against the Angola strain of the related Marburg virus (MARV), with a similar EC50. Injected subcutaneously in mice, SVN reached a peak plasma level of 100nm in 45min, but was cleared within 4h. When ZEBOV-infected mice were given 30mg/kg/day of SVN by subcutaneous injection every 6h, beginning the day before virus challenge, 9 of 10 animals survived the infection, while all infected, untreated mice died. When treatment was begun one hour or one day after challenge, 70–90% of mice survived. Quantitation of infectious virus and viral RNA in samples of serum, liver and spleen collected on days 2 and 5 postinfection showed a trend toward lower titers in treated than control mice, with a significant decrease in liver titers on day 2. Our findings provide further evidence of the potential of natural lectins as therapeutic agents for viral infections.