A European research collaboration has designed a “giant” molecule to inhibit cell infection by Ebola.
Past studies had already demonstrated that the Ebola virus infection process starts when the virus reaches the cellular DC-SIGN receptor to infect the dendritic cells of the immune system.
The research team formed thirteen fullerenes, covered by carbohydrates, to form the large molecule which block this DC-SIGN receptor receptor. The creation proved successful in blocking infection when tested with an artificial Ebola virus model.
“Fullerenes are hollow cages exclusively formed by carbon atoms”, explains Nazario Martín, Professor of Organic Chemistry in the Universidad Complutense de Madrid and main author of the study. In this work, scientists have employed C60 fullerene, which is formed by 60 carbon atoms and has the shape of a truncated icosahedron, which resembles a soccer ball.
These molecules decorated with specific carbohydrates (sugars) present affinity by the receptor used as an entry point to infect the cell and act blocking it, thus inhibiting the infection.
Researchers employed an artificial Ebola virus by expressing one of its proteins, envelope protein GP1, responsible of its entry in the cells. In a model in vitro, this protein is covering a false virus, which is able of cell infection but not of replication.
“We have employed a cell model previously described in our lab which consists in a cell line of human lymphocytes expressing DC-SIGN receptor, which facilitates the entry of the virus in Dendritic Cells”, points out Rafael Delgado, researcher of the Hospital 12 de Octubre, and one of the co-authors of the study.
By blocking this receptor and inhibiting the virus infection, the authors think that the dissemination of the virus would decrease and the immune response increase, but this idea has still to be developed with in vivo studies.
The team has achieved an unprecedented success in fullerene chemistry and dendritic growth: connecting in one synthetic step twelve fullerene units, each with ten sugars, to other central fullerene, creating a globular superstructure with 120 sugar moieties on its surface, “this is the fastest dendrimeric growth developed in a laboratory up to now” says Beatriz Illescas, Professor in the UCM and co-author of the work.
According to scientists, the results highlight the potential of these giant molecules as antiviral agents. “This work open the door to the design and preparation of new systems to inhibit the pathogens infection in cases where the current therapies are not effective or are inexistent, as occurs with the ebolavirus”, clarifies Martín.
After these experiments on the cellular level, researchers will study the behavior of these systems in animal models, starting with mice. “We will study, on the one hand, the pharmacokinetics and, on the other, the antiviral activity in vivo” explains Javier Rojo, researcher of the Instituto de Investigaciones Químicas del CSIC and other of the authors of the study. Once the most effective compound has been identified, studies using the true Ebola virus could be carried out.
Read the study at Nature Chemistry: Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection. DOI: 10.1038/nchem.2387.
