Structure of novel coronavirus spike protein solved in just weeks

In an incredibly fast piece of research, scientists from the University of Texas at Austin and the National Institutes of Health have released a cryo-electron microscopy (cryoEM) structure of part of SARS-CoV-2, the novel coronavirus that has infected tens of thousands of people and killed more than 2,000 since the end of December (Science 2020 DOI: 10.1126/science.abb2507).

The part of the virus imaged, called the spike protein, helps the virus attach to and infect human cells, and its structure comes just weeks after the virus’s genome sequence was published. The breakthrough is a huge step toward developing a vaccine against the virus as well as treatments for COVID-19, the disease that it causes, the researchers say.

UT Austin’s Jason McLellan and his colleagues have spent many years studying other coronaviruses and had already figured out how to use select mutations to lock coronavirus spike proteins into a shape that is conducive for structural studies. After they got the genome sequence of the virus, it took the team just two weeks to design and produce samples of the stabilized spike protein. After collecting data on their stabilized spike protein samples using a cryo-electron microscope, the researchers spent 12 days reconstructing the 3-D structure. They published the results on bioRXiv on Feb. 15, and the paper was rushed through peer review before being published by Science on Feb. 19 (DOI: 10.1126/science.abb2507).

“This is stunning work, illustrating the power of molecular biology in combination with cryoEM,” says Alice Clark, a structural biologist at the University of Wolverhampton. “How quickly this work was possible is a credit to both the scientists involved in this structure, and the recent advances in cryoEM as a technique.”

Coronaviruses are RNA viruses that typically enter human cells when their glycoproteins bind proteins on the cell surface. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) on human cells with higher affinity than does the virus that caused severe acute respiratory syndrome (SARS) in 2003. This difference in affinity possibly explains why the novel coronavirus is more contagious than that other virus. The team is already testing the stabilized spike as a vaccine, and hope the structure will help in the development of antivirals. Similar studies on spike proteins from SARS and Middle East respiratory syndrome (MERS) viruses were used to develop experimental vaccines, but the vaccines never made it to market.