Modified lectin promises new drugs against influenza, HIV and hepatitis C
Bananas contain the protein BanLec, which is effective against several viruses in a modified form. © FreeImages.com / Angel Lior
A single amino acid makes the difference: Thanks to a tiny manipulation, a protein isolated from bananas is effective against flu, hepatitis and AIDS viruses – without the previous side effects. Now the researchers hope to use this as a basis for developing broad-spectrum drugs against viruses, as they report in the magazine "Cell.
Bananas contain a medically highly interesting protein: banana lectin (BanLec) can bind to specific sugar building blocks on the surface of viruses. This causes a virus to no longer be able to enter a cell. Hepatitis C and flu viruses can be stopped, and even the AIDS-causing HIV is stopped by BanLec.
Previously undesirable immune responses
However, BanLec also has an enormous disadvantage: it has a mitogenic effect, which means that it stimulates cells to divide. As this side effect particularly affects the T-cells of the immune system, it leads to undesired immune reactions and inflammation. In the case of HIV, this could also reverse the antiviral effect, since this virus multiplies in T cells – it would then have even more host cells at its disposal.
But a team of researchers led by David Markovitz of the University of Michigan has now made a breakthrough: they studied the structure of the banana protein in order to be able to influence the two mechanisms of action separately. Then they produced a new version of BanLec by molecular genetics. They replaced just one amino acid in the protein chain: at position 84, they exchanged histidine for threonine, thus obtaining the BanLec version H84T.
Altered BanLec protects mice against influenza
This modified version was effective in blood and tissue samples against influenza, AIDS and hepatitis C viruses – and without stimulating T cells to cause inflammation. In experiments on mice, the researchers also showed that H84T protects against infection with influenza.
"Better flu drugs are urgently needed," says Markovitz, who hopes that emergency drugs that can be used quickly will soon emerge from BanLec. "What we’ve done here is exciting because it opens up the possibility of further developing BanLec into a broad-spectrum agent against viruses," says study leader Markovitz. This could be used, for example, to combat epidemics even before the exact pathogen is known.
Overall picture from individual puzzle pieces
Sugar structures like the mannose residues targeted by BanLec are found on many viruses, but the interactions between these sugars and lectins have been little studied. Therefore, H84T also marks a major success in this field: "With the new study, we have managed for the first time to put together individual puzzle pieces of the lectin-sugar interaction to form an overall picture," explains co-author Gabius from Ludwig-Maximilians-Universitat Munich. "This is not only a major advance for drug discovery, but may also take our understanding of the sugar code an important step further."
The modified BanLec is now to be tested on a broad basis against various viruses. Scientists also want to test endogenous lectins to see if they can be optimized for different applications. "One advantage of such tailored lectins would also be that the likelihood of resistance is lower, since sugar structures are more constant than the protein structures of antibodies," says Gabius. ()
(Ludwig Maximilian University of Munich / University of Michigan Health System, 23.10.2015 – AKR)