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

Abstract

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 50 nM, 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 100 nm in 45 minutes, but was cleared within 4 hours. When ZEBOV-infected mice were given 30 mg/kg/day of SVN by subcutaneous injection every 6 hours, 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.

Large-Scale Screening and Identification of Novel Ebola Virus and Marburg Virus Entry Inhibitors

“…Several promising therapeutic candidates are currently being investigated, but none are FDA approved. Strategies such as treatment with antisense oligonucleotides, antibody-based therapies, and treatment with small molecules directed against specific viral as well as cellular factors have been tested, but the outcomes have been mixed (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Additionally, many of these therapies target only closely related strains of Ebola virus, making the development of treatments for other species of Ebola virus and Marburg virus a priority.…”

Cyanobacterial lectins characteristics and their role as antiviral agents

“…Further, in vitro studies show that CV-N can potently inhibit EboZV GP-pseudotyped viruses (EC50 ∼40-60 nmol/L) from mediating gene transduction into HeLa cells and has ability to inhibit DCSIGN from binding to EboZV glycoprotein [145]. Recently, SVN has been reported to exhibit more anti-ZEBOV activity than CVN as it has lower EC 50 (41 nM) than CV-N (154 nM) in tissue culture [46]. In vivo studies exhibits that SVN prevent ZEBOV-infected mice deaths, when treated day before, day on or day after virus challenge, thus might have potential therapeutic role or as prophylactic during human ZEBOV infections [46].…”

“…Recently, SVN has been reported to exhibit more anti-ZEBOV activity than CVN as it has lower EC 50 (41 nM) than CV-N (154 nM) in tissue culture [46]. In vivo studies exhibits that SVN prevent ZEBOV-infected mice deaths, when treated day before, day on or day after virus challenge, thus might have potential therapeutic role or as prophylactic during human ZEBOV infections [46]. SVN binds to ZEBOV envelope glycoprotein and inhibits its replication [29].…”

“…SVN binds to ZEBOV envelope glycoprotein and inhibits its replication [29]. It interacts specifically to the mucin rich region of the enveloped glycoprotein which posses N-linked high-mannose oligosaccharides, thus block viral entry into target cells [46].…”

“…In recent years, many cyanobacterial lectins have been discovered having anti-viral potential and capable of being involved in microbicide development based on their glycan specificity [43]. Cyanobacterial lectins such as cyanovirin-N [45][46][47], microvirin [48], scytovirin [46,49] and Oscillatoria agardii agglutinin [50] are considered as potential candidates to halt virusinfected diseases. Cyanovirin (CVN) a 11 kDa protein derived from cyanobacteria Nostoc ellipsosporum is a potent antiviral agent which mediates its activity through specific and high affinity interactions with glycoproteins present on viral cell surface envelope [51].…”