Article: Computational design of SARS-CoV-2 spike glycoproteins to increase immunogenicity by T cell epitope engineering.
Computational and structural biotechnology journal
2020 Volume 19, Page(s) 518–529
Abstract: ... designed S protein introduced nine new MHC-II T cell promiscuous epitopes that do not exist in the wildtype ... Built on the fact that SARS-CoV-2 utilizes the association of its Spike (S) protein with the human ... the core protein sequence but keep the surface conformation and B cell epitopes. The T cell epitope content ...
Abstract | The development of effective and safe vaccines is the ultimate way to efficiently stop the ongoing COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Built on the fact that SARS-CoV-2 utilizes the association of its Spike (S) protein with the human angiotensin-converting enzyme 2 (ACE2) receptor to invade host cells, we computationally redesigned the S protein sequence to improve its immunogenicity and antigenicity. Toward this purpose, we extended an evolutionary protein design algorithm, EvoDesign, to create thousands of stable S protein variants that perturb the core protein sequence but keep the surface conformation and B cell epitopes. The T cell epitope content and similarity scores of the perturbed sequences were calculated and evaluated. Out of 22,914 designs with favorable stability energy, 301 candidates contained at least two pre-existing immunity-related epitopes and had promising immunogenic potential. The benchmark tests showed that, although the epitope restraints were not included in the scoring function of EvoDesign, the top S protein design successfully recovered 31 out of the 32 major histocompatibility complex (MHC)-II T cell promiscuous epitopes in the native S protein, where two epitopes were present in all seven human coronaviruses. Moreover, the newly designed S protein introduced nine new MHC-II T cell promiscuous epitopes that do not exist in the wildtype SARS-CoV-2. These results demonstrated a new and effective avenue to enhance a target protein's immunogenicity using rational protein design, which could be applied for new vaccine design against COVID-19 and other pathogens. |
---|---|
Language | English |
Publishing date | 2020-12-31 |
Publishing country | Netherlands |
Document type | Journal Article |
ZDB-ID | 2694435-2 |
ISSN | 2001-0370 |
ISSN | 2001-0370 |
DOI | 10.1016/j.csbj.2020.12.039 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.