UC Berkeley and Lawrence Berkeley National Laboratory, or Berkeley Lab, researchers have created a structural map of ORF8, a protein thought to help COVID-19 evade immune system cells.
According to Lee Riley, campus professor and chair of the division of infectious diseases and vaccinology, knowing the structural map of ORF8 can help researchers predict its structure when the protein undergoes mutations and understands how the virus interacts with human cells.
“We still don’t know why some people develop severe disease and die, while many others remain asymptomatic,” Riley said in an email. “There must be other parts of the virus that are contributing to these different clinical outcomes. ORF8 may be one such contributor.”
Researchers generated the structural map using X-ray crystallography, a method for learning the 3D structure of proteins by beaming X-rays at their crystallized forms.
Normally, researchers can compare an unknown protein structure to known amino acids to determine how the protein may fold into a 3D structure. Although ORF8 is a mutated form of a protein found in other coronaviruses, this change influenced the virulence of COVID-19. Therefore, the two proteins do not have comparable structures.
Large parts of nucleic acids can move around through recombination in coronaviruses, according to lead author and campus professor James Hurley. He added that only about half of the protein is related to a known fold type found in an earlier solved structure from other coronaviruses.
“Basically, this mutation caused the protein to double in size, and the stuff that doubled was not related to any known fold,” Hurley said in a press release. “The other half was completely new.”
As a result, campus researchers had to generate hundreds of crystal samples of the protein to send to the Berkeley Lab researchers, who pieced together thousands of diffraction images. This process took around six months.
The team decided to share its findings prior to publication so that other COVID-19 researchers could begin follow-up studies months earlier than they could have otherwise.
Other researchers can use the structural map of ORF8 to develop new drugs and vaccines, Riley added. The technology and algorithms developed to characterize the protein structure can also be used to predict its structure after mutations.
“Because this protein is prone to undergo mutations readily, any drug or vaccine development needs to consider this potential,” Riley said in an email. “This can only be done if we have the tools to predict how the protein structure will change.”
