Researchers Force Viruses to Kill Themselves Via Mutation Rate

As immunity to antibiotics continues to be an issue in the world of viruses, researchers from the University of Chicago (UChicago) and the Massachusetts Institute of Technology (MIT) have found a way to force the stubborn pathogens to eliminate themselves.

Viruses already mutate at a rapid rate, but if they are forced to produce past the threshold then their ability to handle the genetic material diminishes. Documented in the Proceedings of the National Academy of Sciences, the team aimed to understand how an anti-HIV drug causes mutations that fight the disease. They designed lethally mutagenic molecules to simulate actual DNA called KP1212.

“In order to make this work, you need a stealth mutagen,” Andrei Tokmakoff, PhD, professor at UChicago, said in a news release. “You need something sneaky, something that the virus isn’t going to recognize as a problem.”

Previous clinical trials have revealed that KP1212 uses shape shifting, tautomer, to accomplish the resemblance. The investigators found that when the molecules combine with adenine, it forces mutations.

By working with two-dimensional infrared spectroscopy, they were able to not only tell which structures were original or replicas but also the speed of the shape shifting. Under physiological conditions, KP1212 can do so in 20 billionths of a second at a rate of about 50%.

“The research team expected to find only two dominant tautomers, but their experiments showed that many more exist,” the statement revealed. “In addition to taking on different forms as a neutral molecule, KP1212 also could accept an extra proton, giving it a positive charge at physiological levels of acidity—pH of approximately five and a half to seven—that made possible even more rearrangements and tautomer structures.”

The mutations occurred in both protonated and non-protonated forms, however, the rate was lower with the latter. The findings showed that more shape shifters can be created “by decorating the KP1212 scaffold with groups of atoms and molecules” because it increases their ability to obtain protons.

This study can lead to fresh anti-viral treatment options that can tackle hepatitis C, HIV, and other illnesses.

“KP1212 is about 20 percent of the way toward being an ideal therapeutic mutagen,” co-author John Essigmann, PhD, said. "The hints given to us by the spectroscopy guide us toward even better mutagenic molecules.”