Protein can be targeted throughout the COVID-19 variant

According to a team of researchers at Penn State University, a small protein in SARS-CoV-2, the coronavirus that causes COVID-19, can have a significant impact on future treatments.

Scientists have used a new approach to the toolkit to uncover the first complete structure of the nucleocapsid (N) protein and discover how antibodies in COVID-19 patients interact with the protein. did. They also determined that the structure appears to be similar among many coronaviruses, including recent COVID-19 mutants. It is an ideal target for advanced treatments and vaccines.They give their results Nanoscale..

“We have discovered new features in antibody testing and the structure of N proteins that can have a significant impact on the long-term effects of all SARS-related pandemic viruses,” said Professor of Biomedical Engineering and Director of the Penn State University of Structures. Fat Kelly says. Oncology that led the study. “Because the N protein appears to be conserved throughout the SARS-CoV-2 and SARS-CoV-1 variants, treatments designed to target the N protein have been experienced by some people. May help knock out more severe or persistent symptoms. “

Most of the COVID-19 diagnostic tests and available vaccines were designed on the basis of the larger SARS-CoV-2 protein (peplomer), where the virus attaches to healthy cells and initiates the invasion process.

The Pfizer / BioNTech and Moderna vaccines were designed to help recipients produce antibodies that protect them from spelomers. However, according to Kelly, peaplomers can easily mutate, resulting in the emergence of mutants throughout the United Kingdom, South Africa, Brazil, and the United States.

Unlike the outer peplomer, the N protein is virus-encapsulated and protected from the environmental pressures that alter the peplomer. However, the N protein in the blood floats freely after being released from infected cells. Free roaming proteins provoke a strong immune response, leading to the production of protective antibodies. Most antibody test kits look for the N protein to determine if a person was previously infected with the virus. This is in contrast to diagnostic tests that look for spelomers to determine if a person is currently infected.

“Everyone is paying attention to the spike protein, and few studies are being done on the N protein,” said Michael Casasanta, the lead author of the paper and a postdoc at the Kelly Institute. “There was this gap. We saw the opportunity. We had ideas and resources to see what the N protein would look like.”

First, researchers examined N protein sequences from humans, as well as various animals believed to be potential causes of pandemics, such as bats, civets, and pangolins. According to Casa Santa, they all looked similar, but clearly different.

“The sequence can predict the structure of each of these N proteins, but we can’t get all the information from the predictions. We need to confirm the actual 3D structure,” says Casasanta. “We have integrated technology to see new things in new ways.”

Using an electron microscope, researchers used the serum of COVID-19 patients to image both the N protein and the site on the N protein to which the antibody binds, and developed a 3D computer model of the structure. .. They found that the antibody binding site remained the same in all samples, making it a potential target for treating people with any of the known COVID-19 mutants.

“Designing treatments that target the N protein binding site may help reduce inflammation and other persistent immune responses to COVID-19, especially for long-distance transporters of COVID,” Kelly said. He referred to people experiencing the symptoms of COVID-19. 6 weeks or more.

The team procured N-protein purified from RayBiotech Life, a sample containing only N-protein, and applied it to a microchip developed in partnership with Protochips Inc. Microchips are made of silicon nitride instead of traditional porous carbon and are thin wells with a special coating that attracts N proteins to the surface. When ready, the sample was flash frozen and examined with a cryo-electron microscope.

Kelly has advanced Penn State University with microchips, thinner ice samples, and state-of-the-art detectors customized from DirectElectron to provide the highest resolution visualization of lightweight molecules from SARS. We evaluated a unique combination of electron microscopes. -CoV-2 so far.

“The combination of these technologies has made a unique discovery,” Kelly said. “In the past, it was like trying to see something frozen in the middle of a lake. Now I’m looking through an ice cube. I can see smaller entities with more detail and greater precision. . “

Reissued with the courtesy of Pennsylvania State University. Photo: A research team in Pennsylvania found that the N protein of SARS-CoV-2 is conserved in all SARS-related pandemic coronaviruses (top, left: SARS-CoV-2, civet, SARS). -CoV, MERS). This protein is different from other coronaviruses, such as those that cause common colds (bottom, left: OC43, HKU1, NL63, 229E). Credits: Kelly Lab / Penn State