New weapon in the war on animal-borne viruses

As the new coronavirus pandemic spreads, a new study from the Weizmann Institute of Science may help offer an innovative solution to similar cases of animal viruses that infect humans.

Another group of viruses that originate in rodents and sometimes cross over to humans—called arenaviruses—often lead to severe illness including hemorrhagic fevers and meningitis. Weizmann scientists recently devised a decoy for these viruses that may treat infected people and inhibit viruses from infecting humans.

The finding, from the lab of Dr. Ron Diskin in the Department of Structural Biology and led by staff scientist Dr. Hadas Cohen-Dvashi, was published in Nature Communications.

The study focused on a group of viruses within a class of arenaviruses called New World arenaviruses, which originate in South America and North America: Junín, Machupo, Sabiá, and Guanarito. All pathogenic so-called New World arenaviruses make their way into humans via a receptor on the membrane of cells (called the “transferrin receptor 1” or TfR1). To date, research attempts to target viruses like HIV-1 using decoys that mimic the cellular receptor to lure away the virus have used the human version of these receptors, and generally were unsuccessful.

The Diskin lab first found that human cell receptors were not a perfect match for the rodent-borne viruses—which meant that all attempts to mimic the human receptors would never lead to a perfect decoy. So they engineered a molecule that instead uses decoy receptors based on rodent cells—which bind perfectly to the virus. The scientists then engineered that new decoy into an antibody-like molecule, and called it “Arenacept”.

Battle heroes

The good news doesn’t end there. It turns out that not only does Arenacept bind strongly to arenaviruses—it also recruits the immune system to mount an attack against the viral invasion. Think defense and counter-attack.

Moreover, Arenacept is based on the entry point shared by all viruses in a given family—targeting TfR1—rather than on individual characteristics of individual viruses (as is the case of many existing vaccines). Therefore, Dr. Diskin says there is a fair chance that the new molecule will be effective against other arenaviruses that utilize TfR1.

And he expects that it would be safe—although that’s something only clinical trials could determine with certainty. “All signs suggest Arenacept is non-toxic, and that it is also heat-resistant and stable, meaning it would simplify the logistics of delivering it to remote areas of the world where these diseases are endemic,” he says. “And the idea of creating decoys from animal-host receptors might be applied to other viruses that cross to humans from animals.”

The Diskin lab has received a patent for Arenacept and is working with Yeda, the Weizmann Institute’s tech transfer arm, to further develop and commercialize the molecule for clinical use.

Dr. Ron Diskin's research is supported by the Moross Integrated Cancer Center; the Dr. Barry Sherman Institute for Medicinal Chemistry; the Jeanne and Joseph Nissim Center for Life Sciences Research; and the estate of Emile Mimran.