To Stop Viruses, SDSU Researchers are Figuring Out How They're Built

Multiple protein subunits (green, purple and red) of a plant-infecting virus have separate nucleation and growth phases similar to the MS2 bacteria-infecting virus (right).
Source: Protein Data Bank.

An SDSU team, along with Harvard and UCLA collaborators, are researching how distantly related viruses self-organize to improve disease-fighting tactics.

Without a multi-page instruction manual or a commanding Captain America, how do viruses assemble hundreds of individual pieces into elaborate structures capable of spreading disease?

Solving the secret of self-assembly can pave the way for engineering advancements like molecules and robots that put themselves together. It could also contribute to more efficient packaging, automated delivery and targeted design of medicine in the fight against viruses that cause colds, diarrhea, liver cancer and polio.

“If we understand the physical rules of how viruses assemble, then we can try to make them form incorrect structures to hinder their spread,” said Rees Garmann, a chemist at San Diego State University and lead author of a new paper published in the journal PNAS that fills in a piece of the puzzle.

Garmann, along with two SDSU graduate students and collaborators at Harvard and UCLA, concluded that two distantly related RNA viruses — one that infects bacteria and one that infects plants — perform this chemical choreography in strikingly similar ways.

In both, and potentially other, viruses, the protein components perfectly pattern into pentagons and hexagons that form a symmetrical icosahedral shell, the most prevalent shape among all viruses, thanks to a scaffold provided by a looped and folded strand of RNA.

Similar to how a snowflake requires a couple of molecules of frigid water to surround a dust particle before crystallizing, a virus’s jungle-gym-like sphere of proteins coalesces quickly only after a few proteins loosely attach to the RNA.

“Without the interactions between the proteins and the RNA that my students, Fernando Vasquez and Daniel Villareal, were studying, it would take a very long time — weeks, months, maybe never — for this virus to assemble,” Garmann said.

Yet the whole assembly process, which Garmann and his collaborators captured in detailed videos using an innovative microscope that records the movement of individual viruses, takes mere minutes.

“Self-assembly — designing components that know how to get together — is totally different from how we build ordinary things,” Garmann said. “As engineers, we have a lot to learn from viruses.”

Knowing more about how viruses assemble provides clues to the 1950s-era physics paradox of how proteins fold into their proper shapes, which would take longer than the age of the universe if only random chance was at work.

One Case Closed, Others Opened

Although the viruses in this study and the virus that causes COVID-19 both have RNA, the researchers say that extending these findings to the bigger, uglier oddball SARS-CoV-2 virus would be premature.

“The hope of our research is to learn about some physical, fundamental interaction that occurs in these model systems,” said Vasquez, a graduate student in chemistry. “Maybe with more data and time, they can be applied to studying a new virus.”

Source/Credit: San Diego State University | Sarah White and Susanne Clara Bard

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