Synthetic decoy molecule neutralizes a range of animal-to-human viruses.
It is known that arenaviruses are pathogens that infect rodents, and are zoonotic, meaning they can be transmitted between animals and people. Arenaviruses are spread via rodent feces and urine, spreading diseases with two types of clinical presentations, namely neurological and hemorrhagic fever that range in severity. Due to their efficient transmission, arenaviruses pose a high risk for outbreaks with preventative therapeutics sorely needed. Now, a study from researchers at the Weizmann Institute of Science engineers a synthetic protein decoy for these viruses that may keep them from spreading in the body. The team states their decoy molecule neutralizes a range of viruses and points the way toward treating viruses that cross over from animals to humans such as coronaviruses. The opensource study is published in the journal Nature Communications.
Previous studies show immunoadhesin are artificial molecules consisting of protein decoys that mimic viral cellular receptors fused to the fragment crystallizable region (Fc region) of an antibody, which activates the immune system. In theory, these synthetic proteins could be used to intercept viruses by binding to their receptors, luring them away from the human cells. However, attempts to use human-derived receptors as immunoadhesin have so far failed due to low potency. The current study engineers an immunoadhesin using rodent receptors as opposed to human receptors to raise potency that successfully binds to and lures the arenavirus away from human cell receptors.
The current study surgically removes the tip of the rodent’s cell receptors to which the virus binds and engineers it onto part of an antibody to produce an immunoadhesin dubbed ‘Arenacept’. Arenacept was pitted against the Junín and Machupo viruses in lab tests. Results show Arenacept bound strongly to the viruses before the pathogens could bind to the human receptors. Data findings show Arenacept also recruits parts of the immune system to mount an attack against the viral invasion.
The group states as Arenacept utilizes the same universal receptor shared by all viruses in a given family, much like an Apple product using the same charger cable in theory it should be equally effective against all the viruses in the same family that cross to humans from animals. They go on to add that Arenacept may even be effective against viruses from the same family that have not yet been discovered.
The team surmises they have engineered a decoy using rodent receptors that successfully blocked a zoonotic virus from infecting human cells. For the future, the researchers state even though these are the very early stages, data suggests Arenacept is non-toxic, and may also be heat-resistant, meaning it could be delivered to the remote areas.
Source: Weizmann Institute of Science