Due to the current novel coronavirus (nCoV) pandemic, researchers are vigorously rushing to investigate this and other diseases transmitted by animals to humans in an international bid to produce a working vaccine. Arenaviruses are pathogens infecting rodents that 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 ranging 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 designed to prevent them from spreading in the body. The team states their decoy molecule neutralizes a range of viruses and points the way toward treating zoonotic diseases such as coronaviruses. The opensource study is published in the journal Nature Communications.
Previous studies show immunoadhesin are artificial molecules consisting of protein decoys mimicking 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 allowing the artificial molecule to successfully bind to and lure away the arenavirus 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 possessing zoonotic properties. They go on to add Arenacept may even be effective against viruses from the same family not yet discovered.
The team surmises they have engineered a decoy using rodent receptors capable of successfully blocking 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
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