Crystal structure of a neutralizing antibody binding to SARS-COV-2 spike protein

Crystal structure of COVID-19 neutralizing antibody!


As scientists across the globe race to develop a vaccine against SARS-CoV-2, the coronavirus that causes COVID-19, an international team has been working around the clock on a complementary approach - identifying neutralizing antibodies that could be used as a preventative treatment or as a post-exposure therapy.

Their latest findings indicate that antibodies derived from SARS survivors could potently block entry of SARS-CoV-2 and other closely related coronaviruses into host cells. In a study published in Nature, the scientists note that the most promising candidate antibody is already on an accelerated development path toward clinical trials.

"We are very excited to have found this potent neutralizing antibody that we hope will participate in ending the COVID-19 pandemic," said the author.

Neutralizing antibodies are small proteins that inhibit pathogens by binding to the molecule or molecules that the microbe or virus uses to infect host cells. In humans and other animals, special immune cells produce neutralizing antibodies in response to infections, so that if the same pathogen is encountered again the body can eliminate it more quickly. Though natural neutralizing antibodies are typically only produced in the body for a limited time after the initial infection - past research with coronaviruses shows neutralizing antibodies last one or two years - scientists can manufacture pharmaceutical quantities of identical antibodies so long as they know the protein sequence. Mass-produced antibodies may then be given to people who do not yet have any of their own antibodies against that particular pathogen. Vaccines, on the other hand, induce the body to produce its own antibodies by introducing a carefully chosen part of a pathogen - typically a molecule from its outer surface, or a weakened or inert version of the entire pathogen.

Soon after SARS-CoV-2 emerged in late 2019, the authors began screening for potential neutralizing antibodies among those identified from SARS and MERS survivors in 2003 and 2013, respectively. Their previous research on the SARS- and MERS-causing coronaviruses revealed that some neutralizing antibodies produced in response to those diseases were also effective against closely related coronaviruses. So, they suspected that several might inhibit SARS-CoV-2, which is very closely related to SARS-CoV.

The screening yielded eight antibodies that can bind to the SARS-CoV-2 spike glycoprotein - a pyramid-shaped structure on the viral surface, composed of proteins with attached carbohydrates, that facilitates entry into the host cell. Multiple studies have suggested that the spike glycoprotein is the main target for both neutralizing antibodies and vaccines, and vaccines currently in development use a piece of this structure to prime the immune system. Further tests narrowed the field to reveal one SARS-CoV antibody, called S309, that successfully neutralizes SARS-CoV-2.

To understand how this antibody hinders the spike protein, and to gather the information necessary to reproduce it, the team behind the current study used cryo-electron microscopy (cryo-EM) and X-ray crystallography. The group analyzed crystallized samples of S309. These samples are not infectious and posed no safety risk.

"I have been in the field for quite a while and I am still fascinated by the power of protein crystallography," the author added. They show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. 

https://newscenter.lbl.gov/2020/05/19/xray-covid19-antibodies/

https://www.nature.com/articles/s41586-020-2349-y

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fcross-neutralization-of&filter=22

Edited

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