Epitope-Based Potential Vaccine Candidate for Humoral and Cell-Mediated Immunity to Combat Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic

Abstract

The emergence of severe acute respiratory syndrome from novel Coronavirus (SARS-CoV-2) has put an immense pressure worldwide where vaccination is believed to be an efficient way for developing hard immunity. Herein, we employ immunoinformatic tools to identify B-cell, T-cell epitopes associated with the spike protein of SARS-CoV-2, which is important for genome release. The results showed that the highly immunogenic epitopes located at the stalk part are mostly conserved compared to the receptor binding domain (RDB). Further, two vaccine candidates were computationally modeled from the linear B-cell, T-cell epitopes. Molecular docking reveals the crucial interactions of the vaccines with immune-receptors, and their stability is assessed by MD simulation studies. The chimeric vaccines showed remarkable binding affinity toward the immune cell receptors computed by the MM/PBSA method. van der Waals and electrostatic interactions are found to be the dominant factors for the stability of the complexes. The molecular-level interaction obtained from this study may provide deeper insight into the process of vaccine development against the pandemic of COVID-19.

Immunoinformatics mapping of potential epitopes in SARS-CoV-2 structural proteins

“…It is pertinent to note that the predicted continuous B-cell epitopes reported in this study have been previously identified using similar computational tools, and some of the predicted epitopes have now been experimentally validated (Tables 2 – 9 ). Similar findings presented in this work have been reported previously [ 27 – 38 ].…”

“…In this study, we predicted B- and T-cell epitopes using multiple prediction servers by leveraging existing immunological knowledge and the genetic closeness of SARS-CoV-2 with SARS-CoV [ 4 – 6 ]. Previous studies have identified epitopes mainly on the S protein of SARS-CoV-2 ( Table 1 ) using a limited number of prediction servers [ 27 – 38 ]. Using well-established prediction tools, we identified potential B- and T-cell epitopes in the structural proteins (S, E, M, and N) of SARS-CoV-2 ( Fig 1a ).…”

“…A previous computational study has predicted aa656-660 of the S protein and aa60-65 of the E protein as dominant conformational B-cell epitopes [ 37 ], and it is worthy to note that the same epitopes have been predicted in our study ( Table 4 ). A recent study has predicted that conformational epitopes are mainly localized at aa405-427 and aa439-505 regions of the tertiary structure of the S protein [ 38 ]. The highly conserved linear B-cell epitope (aa1253-1273, Table 2 ) predicted in the S protein has been shown to elicit IgG antibodies in some patients with COVID-19 when tested using synthetic peptides spanning aa1256-1273 [ 63 ].…”

“…Therefore, the identification of B-cell and T-cell epitopes of structural proteins is essential for developing effective diagnostic tests and epitope-based vaccine candidates against SARS-CoV-2. Although computational approaches have successfully predicted potential B- and T-cell epitopes, a detailed analysis of epitopes of four structural proteins of SARS-CoV-2 might have important implications in the design and analysis of COVID-19 vaccines under various stages of clinical development [ 27 – 38 ]. Currently, well-developed bioinformatic approaches for epitope analysis have been used to successfully identify epitopes that generate both weak and strong immune responses, which might have been experimentally ignored [ 39 ].…”

Recent Developments in Free Energy Calculations for Drug Discovery

“…El Hassab et al perform fragment based drug design and link together generated fragments binding to RdRp ( El Hassab et al, 2020 ). Potential vaccine candidates derived from B-cell and T-cell epitopes from the spike protein have their binding stability assessed through MD simulation ( Das and Chakraborty, 2020 ).…”