Coronavirus disease 2019 (COVID-19) associated pneumonia caused by severe acute respiratory coronavirus 2 (SARS-COV-2) was first reported in Wuhan, China in December 2019. Till date, no vaccine or completely effective drug is available to cure COVID-19. Therefore, an effective vaccine against SARS-COV-2 is crucially needed. This study was conducted to design an effective multiepitope based vaccine (MEV) against SARS-COV-2. Seven antigenic proteins were taken as targets and different epitopes (B-cell, T-cell and IFN-γ inducing) were predicted. Highly antigenic and overlapping epitopes were shortlisted. Selected epitopes indicated significant interactions with the HLA-binding alleles and 99.29% coverage of the world’s population. Finally, 505 amino acids long MEV was designed by connecting sixteen MHC class I and eleven MHC class II epitopes with suitable linkers and adjuvant. Linkers and adjuvant were added to enhance the immunogenicity response of the MEV. The antigenicity, allergenicity, physiochemical properties and structural details of MEV were analyzed in order to ensure safety and immunogenicity. MEV construct was non-allergenic, antigenic, stable and flexible. Molecular docking followed by molecular dynamics (MD) simulation analysis, demonstrated a stable and strong binding affinity of MEV with human pathogenic toll-like receptors (TLR), TLR3 and TLR8. Codon optimization and in silico cloning of MEV ensured increased expression in the Escherichia coli K-12 system. Designed MEV in present study could be a potential candidate for further vaccine production process against COVID-19. However, to ensure its safety and immunogenic profile, the proposed MEV needs to be experimentally validated.

FN-III proteins are widely distributed in mammals and are usually involved in cellular growth, differentiation, and adhesion. The FNDC5/irisin regulates energy metabolism and is present in different tissues (liver, brain, etc.). The present study aimed to investigate the physiochemical characteristics and the evolution of FN-III proteins and FNDC5/irisin as a ligand targeting the gonadal receptors including androgen (AR), DDB1 and CUL4 associated factor 6 (DCAF6), estrogen-related receptor β (ERR-β), estrogen-related receptor γ (ERR-γ), Krüppel-like factor 15 (KLF15), and nuclear receptor subfamily 3 group C member 1 (NR3C1). Moreover, the putative role of irisin in folliculogenesis and spermatogenesis was also elucidated. We presented the molecular structure and function of 29 FN-III genes widely distributed in the buffalo genome. Phylogenetic analysis, motif, and conserved domain pattern demonstrated the evolutionary well-conserved nature of FN-III proteins with a variety of stable to unstable, hydrophobic to hydrophilic, and thermostable to thermo-unstable properties. The comparative structural configuration of FNDC5 revealed amino acid variations but still the FNDC5 structure of humans, buffalo, and cattle was quite similar to each other. For the first time, we predicted the binding scores and interface residues of FNDC5/irisin as a ligand for six representative receptors having a functional role in energy homeostasis, and a significant involvement in folliculogenesis and spermatogenesis in buffalo.