key: cord-0902853-dj0yhlr6 authors: Ghorbani, Abozar; Zare, Fatemeh; Sazegari, Sima; Afsharifar, Alireza; Eskandari, Mohammad Hadi; Pormohammad, Ali title: Development of a novel platform of virus-like particle (VLP) based vaccine against coronavirus 2019 (SARS-CoV-2) by exposing of epitopes: an immunoinformatics approach date: 2020-10-14 journal: New Microbes New Infect DOI: 10.1016/j.nmni.2020.100786 sha: e2a7a100edbe448482e40865d7c519c245aa0b60 doc_id: 902853 cord_uid: dj0yhlr6 The emergence of a rapidly spreading and highly infectious COVID-19 outbreak by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has caused a global pandemic with unprecedented, social and economic dimensions. Therefore, the development of effective strategies is urgent to control COVID-19 outbreak. According to the recent investigations, cell entry of coronaviruses relies on binding of the viral spike glycoprotein to the host cellular receptors. Therefore, in the present study aimed to predict immunogenic epitopes in silico by analyzed spike protein. In parallel, by screening the immunogenic SARS-CoV-2 spike derived epitopes provided in the literature, we chose a set of epitopes believed to induce immunogenic response. Next, we provided the selected epitopes from both approaches, we performed immunoinformatic analysis that map identically to antigen regions and have antigenic properties. Finally, by suggesting a screened set of epitopes, we designed a novel virus-like particle (VLP) vaccine, optimized to be produced in plants by using molecular farming biotechnology techniques. We anticipate our assay to be a starting point for guiding experimental efforts toward the development of a vaccine against SARS-CoV-2. Angiotensin-Converting Enzyme 2 (ACE2) and uses it as an entry receptor to invade target cells 39 [1] . Therefore, the spike protein of SARS-CoV is anticipated to be an important component of The main information that would help us to choose desirable epitopes is to figure out which parts proteins of SARS-CoV-2 and using bioinformatics tools we suggested a list of potential epitopes 93 for vaccine design. Our findings will potentially narrow down the quest for powerful targets for 94 an effective peptide derived SARS-CoV-2 vaccine and help to direct development-focused 95 studies to achieve a vaccine for COVID-19 infection as soon as possible. Literature review 98 Recent publications related to SARS-COV and SARS-COV2 epitopes were reviewed and the 99 most reliable were selected to choose epitopes [1, 14, 22] . Our main focus and concern to choose 100 epitopes from the researcher's suggestions was their immunogenicity. Potential immunogenic 101 peptides from SARS-COV2 for vaccine targets were selected by screening the most reliable 102 reported conducted since the COVID-19 outbreak was started in early 2020. Epitopes that were 103 more mentioned and repeated in different studies were selected and analyzed carefully. Using immunoinformatics, we could recognize and characterize potential epitopes for the 181 generation of a novel plant-derived VLP-based vaccine [29] . The IEDB is a source of epitope-related information from the scientific literature in the context of infectious disease, allergy, and autoimmunity [30] . The IEDB provides bioinformatics tools and algorithms for analysis of 184 epitope data and prediction of potential epitopes from novel sequences (Fig 1) . A key element in protection against coronaviruses is the neutralizing antibody response. Notably, 186 a previously reported SARS-CoV RBD-specific human neutralizing mAb called CR3022 has 187 been recently noticed to be able to bind to SARS-CoV-2 RBD with high affinity. Evidently, CR3022 recognizes an epitope on the RBD that does not overlap with the ACE2-binding site within the S protein of CoV-2 that concur with our 5 identified epitopes as mentioned in Table 2 . 197 In another approach, we identified multiple specific regions in SARS-CoV-2 spike protein that 198 are ideal candidates as epitopes for vaccine design according to recent studies conducted on 199 SARS-CoV-2, which resulted in finding another five specific epitopes ( Having a high sequence similarity with immunogenic peptides but with greater predicted 202 immunogenicity score our predicted epitopes can be used to build a peptide vaccine (Fig 2) . 203 Also, these epitopes can be used as diagnostic tools for the SARS-CoV-2. We additionally indicate that the designed vaccine model is in good quality (Fig 4) . We predicted the VLP of 216 HBc exposing epitopes of SARS-CoV-2 (Fig 4) . HBc is the best choice as a platform for 217 commercial vaccine production, not only against HBV but also against many other viral diseases. HBc showed high immunogenicity and enhanced presentation to the immune system. This VLP 219 was expressed using an ORF and has the flexibility to allow a wide variety of foreign insertions 220 without affecting the protein self-assembly and VLP function [31, 32] . This result confirmed that have the highest potential to interact with water molecules since they showed the least GRAVY. Overall, a number of epitopes showed to serve as efficient vaccines against SARS-CoV-2 237 infection. However, E29 is predicted to be one of the most promising epitopes, since it has high 238 thermo stability and is strongly hydrophilic. We attempted to find various epitopes against SARS-CoV-2 by using immunoinformatic tools 245 because quick identification of these epitopes is crucial to design vaccine component against 246 COVID-19. Spike protein of SARS-CoV-2, which is currently believed to have the most 247 important role in the binding and entry of these viruses to human cells, was analyzed to find 248 epitopes. We chose five optimal epitopes from the literature and our parallel bioinformatics 249 predictions identified five more epitopes for SARS-CoV-2. These epitopes are the ideal candidate to formulate a multi-epitopic peptide vaccine, not only because of being selected from 251 the ACE2 binding site and CR3022 antibody epitopic regions of spike protein but also because 252 their antigenic property was confirmed by using bioinformatics tools. Based on the selected 253 epitopes, we designed a vaccine to be generated in a short time in the near future. Our novel 254 platform of VLP based vaccine is designed to target the immune response toward these 255 conserved epitope regions which is potent to generate immunity against SARS-CoV-2. 256 Next, the significance and effectiveness of our suggested epitopes as an ideal vaccine candidate 257 against SARS-CoV-2 will be tested in plant-derived VLPs. These immunoinformatic analyses 258 require several in vitro and in vivo validations before designing the vaccine to resist COVID-19. The independent identification of the same regions using two approaches reflects the high 260 probability that our suggested epitopes are promising targets for immune recognition of SARS- Preliminary identification of potential vaccine targets 281 for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies Isolation of a 284 novel coronavirus from a man with pneumonia in Saudi Arabia CoV-2: an emerging coronavirus that causes a global threat Structural and functional basis of 289 SARS-CoV-2 entry by using human ACE2 Puzzle of highly pathogenic human coronaviruses (2019-nCoV) A DNA vaccine 293 induces SARS coronavirus neutralization and protective immunity in mice Characterization of spike glycoprotein of 296 SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV Production and 360 purification of chimeric HBc virus-like particles carrying influenza virus LAH domain as 361 vaccine candidates Engineered hepatitis B core 363 virus-like particle carrier for precise and personalized Alzheimer's disease vaccine preparation 364 via fixed-point coupling Development of 366 epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): 367 Immunoinformatics approach The immune 369 epitope database (IEDB): 2018 update Immune-informatic analysis and design of 371 peptide vaccine from multi-epitopes against Corynebacterium pseudotuberculosis