New coronavirus S protein and cell ACE2 affinity is 10 to 20 times higher than SARS

A few days ago, China’s National Center for Disease Control and Prevention and other research institutions jointly published nearly 9,000 cases of new coronary pneumonia (COVID-19) confirmed cases and suspected cases data show that the basic number of infections of new coronary pneumonia R0 as high as 3.77. Obviously, this new coronavirus (SARS-CoV-2) is much stronger than the SARS virus (R0:0.85-3) in terms of infection alone.

既然新型冠状病毒与SARS病毒都是依赖病毒表面的S蛋白与细胞表面的血管紧张素转换酶2(ACE2)结合,才得以进入细胞,那新型冠状病毒的传染性为什么比SARS病毒强呢?

New coronavirus S protein and cell ACE2 affinity is 10 to 20 times higher than SARS

New Coronavirus Map (Source: NIAID-RML)

Jason S. at the University of Texas at Austin. McLellan’s team, which today published a research paper on the pre-plated platform bioRxiv, gives us a possible explanation.

The McLellan team’s researchers used cryoscope technology to analyze the S-protein structure of the new coronavirus and also used surface plasma resonance (SPR) to analyze the affinity between S protein and ACE2.

They found that the EXtres protein was 10 to 20 times more likely to be associated with the new coronavirus than the SARS virus, rather than the previous one. This also explains why the new coronavirus is so contagious.

Daniel Wrapp and Dr. Wang Nianshuang of the University of Texas at Austin are the first authors of this paper.

New coronavirus S protein and cell ACE2 affinity is 10 to 20 times higher than SARS

From left to right: Daniel, Jason McLellan and Wang Nianshuang (photo source: mclellanlab.org)

Not long after the outbreak of new coronary pneumonia, scientists from the Pasteur Institute in Shanghai, Chinese Academy of Sciences, and the Wuhan Virus Research Institute, respectively, found that the new coronavirus, like SARS virus, also entered the cells by combining the ACE2 protein on the surface of human cells by using S proteins. However, the S protein homologous nature of the two is relatively low, only 76.47%.

Scientists at the Pasteur Institute in Shanghai also used computer models to assess the ability of the S protein sin of the new coronavirus and SARS virus to interact with human ACE2 molecules. It was found that although the s protein and ACE2 of the new coronavirus had less power than the SARS virus, they were still very powerful.

In late January, the NATIONAL Center scare team published a study in the New England Journal of Medicine, based on epidemiological data from 425 patients, and they came up with an R0 value of 2.2, which is broadly consistent with previous studies.

However, as the outbreak spread, new coronary pneumonia showed significantly more infectious than SARS. On Tuesday, the Chinese team assessed r0 value 3.77 based on larger data, essentially making it clear that new coronary pneumonia is more contagious than SARS.

New coronavirus S protein and cell ACE2 affinity is 10 to 20 times higher than SARS

New Coronavirus Map (Source: NIAID-RML)

McLellan is an expert in virus research and has done a lot of very important work on the structure of viruses such as MERS and Ebola.

According to McLellan’s team of researchers, the key to the new coronavirus infection in human cells is the binding of the S protein to the ACE2 protein, to understand the structure of the new coronavirus S protein, and its interaction with ACE2, perhaps to understand why the new coronary pneumonia is more contagious than SARS.

New coronavirus S protein and cell ACE2 affinity is 10 to 20 times higher than SARS

McLellan

To analyze the structure of the S protein of the new coronavirus, McLellan’s team of researchers first synthesized and purified the extrafilm part of the new coronavirus S protein based on the genome sequence that had been made public. The purified S-protein was then taken with a frozen electric mirror, and after 3D reconstruction, the S-protein tripolymer structure with a resolution of 3.5 inches was obtained.

New coronavirus S protein and cell ACE2 affinity is 10 to 20 times higher than SARS

Structure of the new coronavirus S protein

By comparing with the structure of SARS virus, the researchers found that the S protein of the new coronavirus differed from the SARS virus in structure, but overall the similarity was high. From the tripolymer of the S protein, the new coronavirus tripolymer is more likely to bind to the ACE2 protein on the cell surface.

New coronavirus S protein and cell ACE2 affinity is 10 to 20 times higher than SARS

Comparison of the structure of the new coronavirus and SARS virus

To the surprise of McLellan and his colleagues, the results were obtained through surface plasma resonance technology (SPR) analysis. The new coronavirus S protein and ACE2 balance dissohn constant KD is 15 nM, while the balance dissohning of THE SARS virus S protein and ACE2 is 325.8 nM.

As we all know, the higher the KD value, the weaker the affinity between the S protein and ACE2. After calculation, the new coronavirus S protein and ACE2 affinity, is SARS virus S protein and ACE2 between the affinity 10 times, or even 20 times.

Based on this, the researchers believe that it may be the high affinity between the new coronavirus S protein and ACE2, making it easy for the new coronary pneumonia to spread from person to person. Of course, further research is needed to confirm this conclusion.

New coronavirus S protein and cell ACE2 affinity is 10 to 20 times higher than SARS

Comparison of S proteins of new coronaviruses (top) and SARS virus (bottom) with the affinity of ACE2

In summary, McLellan’s team analyzed the structure of the new coronavirus S protein at a higher resolution based on a cryoscope, providing important structural biological data support for the development of subsequent vaccines and antiviral drugs.

The good news is that the new coronary pneumonia vaccine for the S-protein has been tested by the Barney Graham team at the National Institutes of Health’s Vaccine Research and Development Center, a participant in the study.

Expect good news.