Pamela Bjorkman, a Caltech biochemist, asked for volunteers in January 2020 to help her determine the structure of immune proteins that attacked a new coronavirus. This pathogen was discovered in China, and was Severe symptoms resembling severe pneumoniaIt infected the individuals it infected. It would be a significant step towards developing drugs that fight the virus by understanding the molecular arrangement of these antibodies.
Christopher Barnes, a postdoc working in Bjorkman’s lab on the structure of HIV and the antibodies that target it, jumped at the chance to solve a new puzzle. “I was like, ‘Oh, I’ll do it!’” Barnes says. At the time he wasn’t aware how urgent the research would become.
SARS-CoV-2 is a virus that causes COVID-19. We all know this. More than 6 million people have been killed globally. Scientists have been able to quickly develop vaccines for the virus through studies of its structure and antibodies. Saved tens to millions of lives. However, the virus adapts to make changes to the spike protein it uses for cell breakdown. Researchers have been scrambling to find new vaccines and drugs.
Barnes is using high-resolution imaging to study coronavirus spike protein and antibodies. His goal is to find a weak spot that can be exploited to develop a vaccine against all coronaviruses.
Standout research
Barnes’ team used cryo-electron microscopy to reveal the structures of eight antibodies that stop the original version of SARS-CoV-2. This technique freezes proteins, viruses, and cells as they go about their daily business. In this instance, the team isolated coronavirus particles from COVID-19 patients.
The antibodies had attached to four spots on the spike protein’s receptor binding domain, or RBD, the team reported in Nature2020. This finger-shaped region anchors the virus to any cell it infects. Antibodies that bind to this region will prevent the virus from attaching to the cell.
Barnes’ team also created an antibody classification system based on the RBD location where the immune system proteins tend to latch on. “That’s been really helpful for understanding the types of antibody responses that are elicited by natural infection,” says structural biologist Jason McLellan, who wasn’t involved in the work, and for identifying prime candidates for drug development.
“A major strength of Chris is that he does not limit himself or his research to one technique,” says McLellan, of the University of Texas at Austin. “He quickly adapts and incorporates new technologies to answer important questions in the field.”
Barnes and six of his Stanford collaborators have worked together to determine the structure of six different structures since he started his own lab. antibodiesThese viruses attack the original SARS/CoV-2 virus. deltaAnd Omicron variants. They are capable of evading antibodies, even lab-made ones that have been given to patients for COVID-19.
The newly identified antibodies were described in the June 14th issue. Immunity, target the spike protein’s N-terminal domain. The structure of the protein attachment sites is the same in both delta and omicron. This suggests that these sites may remain the same even in future versions, the team claims. Scientists may eventually be able mass-produce antibodies targeting these sites to aid in developing new therapies.
What’s next
Barnes has now turned his attention to antibodies that can fend off all coronaviruses — from ones that cause the common cold to ones found in livestock and other animals that have the potential to spill over into people.
Barnes and immunologist Davide Robbiani of the University of Lugano in Switzerland identified classes of antibodies that target variants from all four coronavirus families, blocking the viruses’ ability to fuse with cells.
What’s more, the structure of one of the binding sites on the spike protein is the same across the coronavirus family tree, Barnes says. “This is something you wouldn’t want to mutate as you diversify your viral family because this is a critical component of how you enter the cell.”
Two separate teams found similar broad activity in the same class of antibodies. Barnes believes that the results can be combined to create a universal coronavirus vaccination.
“We’ve all kind of discovered this at the same time,” he says. The teams are now thinking, “Wow, this exists. So let’s try to make a real, true pan-coronavirus vaccine.”
You would like to nominate someone on the next SN 10 List? Please send your name, affiliation, and a few sentences about yourself and your work to sn10@sciencenews.org.
