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A host of disease-causing viruses called arenaviruses lurk in animal populations in various parts of the world, sometimes crossing over into humans. When they do cross over, they can be lethal, and only very few treatments exist. Researchers led by scientists at the Weizmann Institute of Science have now devised a clever decoy for these viruses that may keep them from spreading in the body. Two disease-causing arenaviruses, known as Junín and Machupo, circulate through rodent populations, mainly in South America, and they can infect humans when people come in contact with affected rodents. Similar to Ebola, these diseases can cause the body to "bleed out," and the only treatments, to date, are risky and complex, as they are taken from the blood of survivors.
The present study, which was reported in Nature Communications, arose from an earlier research question in the group of Dr. Ron Diskin of the Institute's Structural Biology Department: how are certain arenaviruses able to move from rodents or other animals into humans? Comparing these viruses with members of the arenavirus family that are not infectious to humans, the researchers noted that the non-infectious viruses did not completely fit a particular receptor - a protein complex on the cell membrane - that serves as a viral entry point into human cells. But curiously, those that do infect humans were also not a perfect fit. They were just good enough to get by. This observation led to another insight: Maybe the rodent cell receptors, which were a much better fit to the "entry" proteins on the viruses, could be used to intercept the viruses and lure them away from the human cells. There had been earlier attempts to develop such decoys - "sticky" molecules designed to attract virus proteins - explains Diskin, but these were based on the structures of human receptors, so they were identical to the ones on the body's cells and thus unable to compete effectively. In contrast, a molecule based on a rodent receptor, he and his team reasoned, could far outcompete the human ones for binding to the virus.
Dr. Hadas Cohen-Dvashi, in Diskin's group, led the next stage of the research, in which she "surgically removed" the very tip of the rodent receptor to which the virus binds and engineered it onto part of an antibody. The newly resulting molecule was called "Arenacept." Then the group began testing this molecule - at first against "pseudoviruses," engineered virus-like complexes which carry the entry proteins but that are not dangerous. Already at this stage, and in collaboration with the group of Dr. Vered Paler-Karavani of Tel Aviv University, the researchers noted that Arenacept not only bound strongly to the viruses, it recruited parts of the immune system to mount an attack against the viral invasion....
Published in Nature Commun. (January 3, 2020):
