
No specific treatment is approved for COVID-19, until now. Also, the accessory proteins (n = 8) play key roles in the virus assembly, virulence and pathogenesis. The envelop (E), membrane (M), nucleoprotein (N) and spike (S) are the structural proteins which assemble the virus particle. The non-structural proteins (nsp1-nsp16) are only produced during the virus RNA translation at the infected host cells. Its genome encodes 28 proteins which are divided into three categories including non-structural (nsp), structural, and accessory proteins. SARS-CoV-2 is an enveloped positive-strand RNA virus. It causes a severe respiratory disease called COVID-19 and global health currently is facing its devastating outbreak. SARS-CoV-2 is a newly identified member of the coronavirus family. Although the designed vaccine exhibited high efficacy in silico, further experimental validation is necessary. At last, the final vaccine construct was reverse translated to design the DNA vaccine. Global population coverage of the vaccine for HLA-I and II were estimated 96.2% and 97.1%, respectively. It could form stable and significant interactions with TLR-4/MD according to molecular docking and dynamics simulations. The final vaccine construct was an immunogenic, non-allergen and unfunctional protein which contained multiple CD8 + and CD4 + overlapping epitopes, IFN-γ inducing epitopes, linear and conformational B cell epitopes. The physicochemical properties, allergenicity, antigenicity, functionality and population coverage of the final vaccine construct were analyzed. Also, a CD4 + T-helper epitope, PADRE, was used at the C-terminal of the vaccine by GPGPG and A(EAAAK)2A linkers to form the final vaccine construct. Moreover, the functional region of β-defensin as a well-known agonist for the TLR-4/MD complex was added at the N-terminus of the vaccine using (EAAAK)3 linker. The selected regions’ sequences were connected to each other by furin-sensitive linker (RVRR). Also, immunodominant fragment of the functional region of SARS-CoV-2 spike (400–510 residues) protein was selected for inducing neutralizing antibodies production. The immunodominant regions of six non-structural proteins (nsp7, nsp8, nsp9, nsp10, nsp12 and nsp14) of SARS-CoV-2 were selected by multiple immunoinformatic tools to provoke T cell immune response. In this study, a novel multi-epitope vaccine against SARS-CoV-2 was designed to provoke both innate and adaptive immune responses. However, there is no vaccine available against this virus up to now. Currently, global health is facing its devastating outbreak.

SARS-CoV-2 causes a severe respiratory disease called COVID-19.
