Coronaviruses, such as the one that causes the current outbreak of COVID-19, have glycoprotein “spikes” on their surface. These spikes help the virus to enter host cells by fusing the virus and cell membranes. This important function makes the spike proteins promising targets for medical treatments.
Jason S. McLellan, The University of Texas at Austin, USA, and colleagues have determined the structure of the extracellular part of the spike protein of the coronavirus that causes COVID-19. The team used the previously reported genome sequence of the virus to produce the spike protein using a human cell line. They introduced two mutations to stabilize the expressed protein. The team then used cryogenic electron microscopy (cryo-EM) to obtain a 3D reconstruction of the protein (pictured) with a resolution of 3.5 Å. Cryo-EM uses very low temperatures to allow the determination of biomolecular structures at almost atomic resolution.
The team found that the protein consists of two subunits, one of which is the receptor-binding domain (RBD) that interacts with host cells. The protein exists as a trimer, with one of the three RBDs (pictured in green) rotated up in its most common configuration. Since the structure of the spike protein resembles that of the SARS coronavirus, the team tested whether antibodies targeted at SARS could bind to the spike protein of the new coronavirus. No binding was detected, which means that antibodies more specific to the new coronavirus need to be developed.
According to the researchers, using the characterized spike protein as a probe could help to isolate antibodies for COVID-19 treatment. The results might also be useful for the development of vaccines and small-molecule drugs to fight the disease.
- Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation,
Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett, Jory A. Goldsmith, Ching-Lin Hsieh, Olubukola Abiona, Barney S. Graham, Jason S. McLellan,
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