Researchers at Ludwig Maximilian University of Munich (LMU; Germany) have modified a banana protein with a single amino-acid substitution, successfully converting it into a promising new antiviral agent. A sugar-binding protein in bananas, called BanLec, has already been shown to be a protein inhibitor of several pathogenic viruses in humans. BanLec binds to the sugar molecules on viral coat proteins, blocking viruses from entering host cells.
However, BanLec acts as a mitogen, activating cell proliferation, which could lead to deleterious side-effects. The team at LMU has demonstrated that BanLec can be modified to retain its antiviral properties while eliminating the mitogenic effects. Hans-Joachim Gabius, one of the leaders of the study, believes that his team’s findings could pave the way to a novel class of antiviral agents.
“It could facilitate the development of custom-made tools for further investigation of the mechanisms that underlie sugar-protein interactions, which are still poorly understood,” Gabius explained. BanLec is a lectin that binds to glycan structures containing the monosaccharide mannose. Gabius continued, “Since other viruses, such as hepatitis C viruses, corona viruses and influenza viruses, also bear mannose units in their envelope proteins, BanLec could provide the basis of a broad-spectrum antiviral agent.”
The mitogenic effect of BanLec requires its simultaneous binding to two distinct receptors. The team disabled this effect by substituting the amino acid threonine for the histidine usually found at a specific position in the lectin. The modified lectin retains the ability to prevent infection by HIV, hepatitis C and influenza.
The next stage of research will be to test the effects of the modified BanLec on a broad range of viruses. To gain further insight into the lectin’s mode of action, Gabius will focus on identifying the sets of receptors recognized by the natural and modified versions of BanLec. The researchers will also take a closer look at human lectins, and hope to optimize their properties for various applications.
Swanson, M. D., Boudreaux, D. M., Salmon, L., Chugh, J., Winter, H. C., Meagher, J. L., … Markovitz, D. M. (2015). Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity. Cell, 163(3), 746–758. doi:10.1016/j.cell.2015.09.056