UC Berkeley researchers helped publish a study June 22 looking into the structure of a new protein expressed by the SARS-CoV-2 ORF3a gene, the discovery possibly leading to further strides against COVID-19.
The study, which was largely funded by the Fast Grants organization, found that one of the virus’s three proteins, the 3a protein, is unlike those that have been previously discovered, according to David Kern, a researcher for the study. Researchers also discovered that removal of the protein stifles the virus’s replicating efforts, making it a candidate for future vaccines.
“Of the accessory proteins, 3a seems like the one that is the most important to the virus’s function,” Kern said.
Kern used cryogenic electron microscopy and Thermo Fisher Scientific’s microscope technology to visualize the protein, a technical feat given its small size. The resulting image revealed a unique structure, according to Kern.
Research on the protein began in 2020, when the genome of SARS-CoV-2 was made public, according to a Berkeley News article.
“We started to look at it, thinking this is an interesting virus and thought it could become more serious than it seemed at the time,” said Stephen Brohawn, assistant professor in the campus department of molecular and cell biology and a research supervisor. “We found from work on SARS-CoV-1 that 3a might be an interesting target for therapeutics or vaccine development.”
The protein produced by ORF3a appears to be an ion channel, conducting positively charged ions across a cell membrane — allowing the signaling of pathways in the cell, according to the study.
Whereas most known ion channels fully cross through the membrane, the 3a protein only pierces halfway, according to the Berkeley News article. Its ions appear to trace the outside of the protein and continue across the membrane.
Campus researcher Ben Sorum measured the currents across the 3a protein channel.
“The whole idea was that — through the electrophysiology I was doing — we would be able to discover a specific drug that would block the 3a viroporin, and it would be a type of therapy given to individuals,” Sorum said.
Sorum noted that patients eligible to receive the drug in the future would include those who were unable to receive the COVID-19 vaccine.
Given further research into the 3a structure, drugs can be tested for their ability to impact the viral life cycle, according to Sorum.
“We’re very curious to find ways to push the protein to adapt the other kind of shapes that it does when it’s functioning in a cell … to understand how it works and moves,” Brohawn said.
The ORF3a gene is found in “a majority of coronaviruses,” Kern added. In the future, others will likely have the 3a protein, making the study’s findings significant to furthering drug and therapeutic developments.