Abstract
The occurrence of the SARS-CoV2 infection has become a worldwide threat and the urgent need to discover therapeutic interventions remains paramount. The primary roles of the coronavirus nucleocapsid (N) protein are to interact with the viral genome and pack them into ribonucleoprotein complex. It also plays critical roles at many stages of the viral life cycle. Herein, we explore the N protein of SARS-CoV2 to identify promising epitope-based vaccine candidates and target the N-terminal domain of SARS-CoV2 N-protein for potential inhibitors using an integrative bioinformatics approach. We identified B-cell epitopes and T-cell epitopes that are non-toxic, non-allergenic, capable of inducing IFN-γ and structurally stable with high global population coverage of response. The 404 SKQLQQSMSSADS 416 and 92 RRIRGGDGKMKDL 104 sequences of N-protein were identified to induce B-cell immunity. We also identified 79 SSPDDQIGY 87 and 305 AQFAPSASAFFGMSR 319 as potential T-cell epitopes that form stable structures with human leucocyte antigens. We have also identified zidovudine triphosphate, an anti-HIV agent, as a potential inhibitor of the N-terminal domain of SARS-CoV2 N-protein based on docking and simulation analysis and should be considered for experimental validations. The findings of this study can help fast-track the discovery of therapeutic options to combat COVID-19.
Keywords: COVID-19; Epitope; Immuno-informatics; Molecular dynamics simulation; Vaccine; Zidovudine.
【저자키워드】 COVID-19, Vaccine, Molecular dynamics simulation, epitope, Immuno-informatics, zidovudine, 【초록키워드】 Structure, coronavirus, SARS-CoV2, Immunity, bioinformatics, docking, molecular dynamics, SARS-CoV2 infection, Molecular dynamics simulation, Protein, Epitopes, Coverage, Viral, nucleocapsid, N protein, antigens, B-cell epitope, inhibitor, B-cell epitopes, T-cell epitopes, epitope, Critical, T-cell epitope, IFN-γ, B-cell, N-terminal domain, therapeutic options, Immuno-informatics, Analysis, viral genome, Epitope-based vaccine, ribonucleoprotein, leucocyte, therapeutic option, life cycle, zidovudine, zidovudine triphosphate, complex, non-allergenic, sequence, help, Stage, candidate, therapeutic interventions, therapeutic intervention, viral life cycle, N-protein, approach, non-toxic, Occurrence, identify, induce, the N protein, 【제목키워드】 SARS-CoV2, Drug discovery, nucleocapsid protein, targeting,