Vaccine may need to dig a little deeper to stop SARS-CoV-2. Rice University researchers are providing a new shovel.
Rice computer scientists developed SARS-Arena to help find conserved parts of a protein from SARS-CoV-2 that could be key to developing a broad-spectrum vaccine. The program looks for potential matches between regions in the nucleocapsid protein (N) and human leukocyte antigen (HLA) receptors that are central to cellular immunity. Illustrated by Mauricio Menegatti Rigo / Rice University
Computer Scientist’s Lab Lydia Kavraki at Rice’s George R. Brown School of Engineering introduced a program to search for the conserved protein parts of the virus that cause COVID-19. These organs could help develop future vaccines.
Lab’s open source program, SARS-Arenaidentify peptides that are part of the virus nucleocapsid proteins to see how they might be targeted. Kavraki says the program was designed from the ground up to be highly customizable and easy to use.
“Our work did not analyze the spike protein on the surface of the SARS-associated coronavirus but a protein deep within the core of such viruses,” said Kavraki. “We have identified and systematized a complex process for uncovering fragments of that protein that could serve as the basis for the development of new vaccines.”
Rice University graduates, from left, Anja Conev, Romanos Fasoulis and Sarah Hall-Swan and postdoctoral researcher Mauricio Menegatti Rigo worked on the development of SARS-Arena, a program to help find Conserved parts of the protein from SARS-CoV-2 could be the key to the development of broad-spectrum vaccines. Image credit: Rice University
Details about SARS-Arena appear in Borders in Immunology. The program can be found here: https://github.com/KavrakiLab/SARS-Arena.
The program builds on the established laboratory HLA-Arenaa customizable pipeline for structural modeling and analysis of complexes made up of peptides – small parts of proteins – and Human leukocyte antigen (HLA) receptor, central to cellular immunity.
The SARS-CoV-2 nucleocapsid protein is compact and hidden within the SARS envelope, where it helps to package the viral genome. This protein is highly conserved for the SARS virus, and because it is located in the interior of the virus, it is also less prone to mutating than proteins along the surface envelope, especially the mutated protein that is most commonly detected. Current COVID vaccines target.
According to lead author and postdoctoral researcher Mauricio Menegatti Rigo, surface proteins are the moving target of vaccines. The omicron The variant has more than 30 mutations in just the mutant protein, and that probably contributed to its rapid infection rate.
Nucleocapsid proteins are highly expressed during infection. That also increases the chance for the immune system to spot them and move on. Nucleocapsid is very immunitymaking them capable of triggering an immune response.
But not all well-conserved peptide “hooks” in the nucleocapsid are known, nor are there enough data on how they bind to HLA. Identifying more of them can aid in long-term, broad-spectrum searches Coronavirus Rigo said.
“We are primarily interested in the activated cellular immune response against nucleocapsid peptides,” he said. “So the first part of the paper is about identifying these conserved peptides. In the second part, we provide a way to analyze not only the sequence of the peptides, but also how they can bind to HLA molecules.
“We can then look for clues about how the peptides are presented in the context of the immune response,” says Rigo. “We show that through structural analysis we can identify cross-reactive peptides and also similar peptides that are capable of cross-reactivity. These same peptides not described in the literature are new putative targets for vaccines.”
There are studies showing that immune system T cells taken from recovered COVID-19 patients can recognize multiple regions of the nucleocapsid protein, providing long-term protective immunity. So finding peptide targets inside the nucleocapsid has become a worthy goal, says Rigo.
The new work is a continuation of the Rice team’s efforts to simplify the search for a coronavirus vaccine. In a November 2020 paper published in the Proceedings of the National Academy of Sciences, researchers identified a SARS-CoV-2 . peptide affects the immune system’s receptor-binding stability, affecting the body’s ability to attack diseased cells. Other paper published in june by Nature’s Science Report improved their algorithm for predicting the binding affinity between peptide and HLA structures. That research has implications for the development of both virus and cancer vaccines.
Rice alumni Dinler Amaral Antunes, now an associate professor of computational biology at the University of Houston, is a co-author of the paper. Co-authors are Rice PhD students Romanos Fasoulis, Anja Conev and Sarah Hall-Swan. Kavraki is Noah Harding’s Professor of Computer Science and professor of bioengineering, mechanical engineering, and electrical and computer engineering, and director of the Ken Kennedy Institute.
Source: Rice University
