Researchers from the University of Texas at Austin and the National Institutes of Health (NIH) have made a critical breakthrough towards developing a vaccine for the 2019 novel coronavirus, SARS-COV-2 (initially called 2019-nCoV), by creating the first 3D atomic scale map of the part of the virus that attaches to and infects human cells. This is the protein that appears as spikes on the virus envelope, the basis for the adjective “corona” .
During viral entry, the SARS-COV-2 makes use of the spike (S) protein to recognise a host receptor and drive the fusion of the viral envelope with the target cell membrane. Binding triggers a structural change of the S protein that facilitates membrane fusion. The S protein is thus an important target for therapy, and the characterisation of its structure before fusion would provide researchers information to guide vaccine design and development as well as the production of antiviral drugs for therapy. This work has been published in the latest issue of the journal “Science”. The team is also working on a viable candidate vaccine based on the map.
The team, led by Jason McLellan of UT at Austin, has vast experience in studying other coronaviruses, including SARS-CoV and MERS-CoV, and had already developed methods for locking coronavirus spike proteins into a shape that made them easier to analyse and could effectively turn them into candidates for vaccines.
Just two weeks after receiving the genome sequence of the virus from Chinese researchers, the team designed and produced samples of their stabilised spike protein. It took 12 more days to reconstruct the 3D atomic scale map, called a molecular structure, of the spike protein and submit the paper to “Science”, which expedited its peer review process.
Here, using the reported genome sequence of SARS-COV-2 to make and purify viral proteins for analysis, the researchers have determined a “cryo-EM” structure of the S protein at 3.5 angstrom resolution using the state-of-the-art technology of cryogenic electron microscopy. Their analysis confirms the predicted similarity to the SARS coronavirus spike.
However, the authors also report that the affinity of the SARS-COV-2 S protein for human ACE2, the entry point into human cells for some coronaviruses, is ten times higher than in the case of SARS. This possibly explains the apparent ease of human-to-human transmission of SARS-COV-2, although more studies are needed to investigate this possibility.
McLellan’s team plans to use their molecule to pursue another line of attack against the virus that causes the disease COVID-19, using the molecule as a “probe” to isolate naturally produced antibodies from SARS-COV-2 patients who have recovered fully. In large enough quantities, these antibodies could help treat a coronavirus infection soon after exposure. For example, the antibodies could protect healthcare workers sent into an area with high infection rates at short notice.
