Abstract
The causative agent of severe acute respiratory syndrome (SARS) reported by the Chinese Center for Disease Control (China CDC) has been identified as a novel Betacoronavirus (SARS-CoV-2). A computational approach was adopted to identify multiepitope vaccine candidates against SARS-CoV-2 based on S, N and M proteins being able to elicit both humoral and cellular immune responses. In this study, the sequence of the virus was obtained from NCBI database and analyzed with in silico tools such as NetMHCpan, IEDB, BepiPred, NetCTL, Tap transport/proteasomal cleavage, Pa3P, GalexyPepDock, I-TASSER, Ellipro and ClusPro. To identify the most immunodominant regions, after analysis of population coverage and epitope conservancy, we proposed three different constructs based on linear B-cell, CTL and HTL epitopes. The 3D structure of constructs was assessed to find discontinuous B-cell epitopes. Among CTL predicted epitopes, S257-265, S603-611 and S360-368, and among HTL predicted epitopes, N167-181, S313-330 and S1110-1126 had better MHC binding rank. We found one putative CTL epitope, S360-368 related to receptor-binding domain (RBD) region for S protein. The predicted epitopes were non-allergen and showed a high quality of proteasomal cleavage and Tap transport efficiency and 100% conservancy within four different clades of SARS-CoV-2. For CTL and HTL epitopes, the highest population coverage of the world’s population was calculated for S27-37 with 86.27% and for S196-231, S303-323, S313-330, S1009-1030 and N328-349 with 90.33%, respectively. We identified overall 10 discontinuous B-cell epitopes for three multiepitope constructs. All three constructs showed strong interactions with TLRs 2, 3 and 4 supporting the hypothesis of SARS-CoV-2 susceptibility to TLRs 2, 3 and 4 like other Coronaviridae families. These data demonstrated that the novel designed multiepitope constructs can contribute to develop SARS-CoV-2 peptide vaccine candidates. The in vivo studies are underway using several vaccination strategies.
Highlights
The causative agent of severe acute respiratory syndrome (SARS) reported by the Chinese Center for Disease Control (China CDC) has been identified as a novel Betacoronavirus (SARS-CoV-2) [1]
The entry of SARS-CoV-2 into host cells is mediated by attachment of S glycoprotein on the virion surface to the angiotensin-converting enzyme 2 (ACE2) receptor [3] mainly expressed in type 2 alveolar cells of lungs [4]
These immunoinformatics methods have made a significant impact on the immunology researches and we can see many examples of in silico design of epitope-based vaccines against many viruses including human immunodeficiency virus (HIV) [16], human papillomavirus (HPV) [38, 39], SARS-CoV [40], rhinovirus [41]
Summary
The causative agent of severe acute respiratory syndrome (SARS) reported by the Chinese Center for Disease Control (China CDC) has been identified as a novel Betacoronavirus (SARS-CoV-2) [1]. Genomic RNA of SARS-CoV-2 encodes non-structural replicase polyprotein and structural proteins including spike (S), envelope (E), membrane (M) and nucleocapsid (N). The entry of SARS-CoV-2 into host cells is mediated by attachment of S glycoprotein on the virion surface to the angiotensin-converting enzyme 2 (ACE2) receptor [3] mainly expressed in type 2 alveolar cells of lungs [4]. Enhanced binding affinity between SARS-CoV-2 and ACE2 receptor was proposed to correlate with increased virus transmissibility [5]. The trimeric S protein will be cleaved into two subunits of S1 and S2 during viral infection [6]. S1 and S2 subunits are responsible for binding to the ACE2 receptor and the fusion of the viral and cellular membranes, respectively [3]. Being the main antigenic component, S protein has been selected as an important target for vaccine development
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