Scientists "outsmart Mother Nature" to combat deadly virus

In the atomic structure of the coxsackievirus B3 polymerase, the researchers replaced the phenylalanine 364 (orange) with a tryptophan (turquoise), reducing the ability of the virus to replicate(Credit: Olve Peersen/Colorado State University)

Coxsackievirus B can be deadly, leading to heart disease and, in some cases, death. Now scientists at Colorado State University (CSU) have developed a method to combat the virus. Described as a "genetic poison pill," the technique restricts the ability of the virus to replicate and can even cause it to self-destruct. The approach could one day lead to a vaccine against coxsackievirus B and similar viruses.

Led by CSU professor Olve Peersen, previous research into how coxsackievirus copies itself and mutates focused on the RNA-dependent RNA polymerase responsible for replication. For this follow-up project, Peersen and the team worked with the specific strain, coxsackievirus B3, and modified that replicating polymerase so it fights against itself.

As the polymerase replicates the virus genome, it makes several random mistakes in order to continue evolving. The researchers were able to "outsmart Mother Nature," as Peersen puts it, by swapping out one amino acid in the polymerase for another, resulting in a checkmate effect on the virus.

The introduced amino acid, a tryptophan, reduced the polymerase's ability to make mutations, which reduced its ability to replicate. Additionally, if the virus mutates to remove the change, it essentially self-destructs as it is then unable to replicate.

This method also holds the potential for the development of vaccines against coxsackievirus B3 and other positive-sense RNA viruses, including poliovirus, dengue, Zika, as well as those linked to hand, foot and mouth disease and asthma in humans, and foot-and-mouth disease in animals.

"We think it's going to work, but we have to show that it will," says Peersen. "Trying to outsmart Mother Nature is pretty daunting, especially in these viruses. There are ways that things happen you never anticipate, and the virus finds a way to survive."

The research appeared in The Journal of Biological Chemistry, and Peersen and the team are clear to begin testing the method in animals.

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