Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus 2 (SARS-COV-2) is a significant threat to global health security. Till date, no completely effective drug or vaccine 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 highly antigenic proteins of SARS-COV-2 were selected as targets and different epitopes (B-cell and T-cell) were predicted. Highly antigenic and overlapping epitopes were shortlisted. Selected epitopes indicated significant interactions with the HLA-binding alleles and 99.93% coverage of the world’s population. Hence, 505 amino acids long MEV was designed by connecting 16 MHC class I and eleven MHC class II epitopes with suitable linkers and adjuvant. MEV construct was non-allergenic, antigenic, stable and flexible. Furthermore, molecular docking followed by molecular dynamics (MD) simulation analyses, demonstrated a stable and strong binding affinity of MEV with human pathogenic toll-like receptors (TLR), TLR3 and TLR8. Finally, MEV codons were optimized for its in silico cloning into Escherichia coli K-12 system, to ensure its increased expression. 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.

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Background Coronavirus disease 2019 (COVID-19) linked with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause severe illness and life-threatening pneumonia in humans. The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection. Therefore, the present study was aimed to design a multiepitope-based subunit vaccine (MESV) against COVID-19. Methods Structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) of SARS-CoV-2 are responsible for its prime functions. Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B- and T- cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV. Results Predicted epitopes suggested high antigenicity, conserveness, substantial interactions with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 88.40%. Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers. The MESV construct was non-allergenic, stable, and highly antigenic. Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3 (TLR3). Furthermore, in silico immune simulation revealed significant immunogenic response of MESV. Finally, MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system, to ensure its increased expression. Conclusion The MESV developed in this study is capable of generating immune response against COVID-19. Therefore, if designed MESV further investigated experimentally, it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19.

1Coronavirus disease 2019 (COVID-19) associated pneumonia caused by severe acute respiratory 2 coronavirus 2 (SARS-COV-2) was first reported in Wuhan, China in December 2019. Till date, 3 no vaccine or completely effective drug is available for the cure of COVID-19. Therefore, an 4 effective vaccine against SARS-COV-2 is needed to be design. This study was conducted to 5 design an effective multi-epitope vaccine (MEV) against SARS-COV-2. Seven antigenic 6 proteins were taken as a target and epitopes (B cell, IFNγ and T cell) were predicted. Highly 7 antigenic and overlapping epitopes were shortlisted. Selected T cell epitopes indicated significant 8 interactions with the HLA-binding alleles and 99.29% coverage of the world's population. 9 Finally, 505 amino acids long MEV was designed by connecting sixteen MHC class I and twelve 1 0 MHC class II epitopes with suitable linkers and adjuvant. Linkers and adjuvant were added to 1 1 enhance the immunogenicity response of the vaccine. The allergenicity, physiochemical 1 2 properties, antigenicity and structural details of MEV were analyzed in order to ensure safety and 1 3 immunogenicity. MEV construct was non-allergenic and antigenic. Molecular docking 1 4 demonstrated a stable and strong binding affinity of MEV with TLR3 and TLR8. Codon 1 5 optimization and in silico cloning ensured increased expression in the Escherichia coli K-12 1 6system. However, to ensure its safety and immunogenic profile, the proposed vaccine needs to be 1 7 experimentally validated. 1 8

Background: Coronavirus disease 2019 (COVID-19) caused by Severe Acute RespiratorySyndrome Corona virus 2 (SARS-COV-2) was first diagnosed in December 2019, Wuhan, China. Little is known about this new virus and it has the potential to cause severe illness and pneumonia in some people, therefore the development of an effective vaccine is highly desired.Methods: Immunoinformatics and statistical approaches were used in this study to forecast B-and T-cell epitopes for the SARS-COV-2 structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) that may play a key role in eliciting immune response against COVID-19. Different types of B cell epitopes (linear as well as discontinuous) and T cell (MHC class I and MHC class II) were determined.Moreover, their antigenicity and allergenicity were also estimated. Results:The antigenic B-cell epitopes exposed to the outer surface were screened out and 23 linear B cell epitopes were selected. "SPTKLNDLCFTNVY" had the highest antigenicity score among B cell epitopes. The T-cell epitopes bound to multiple alleles, antigenic, non-allergen, non-toxic, and conserved in the protein sequence were shortlisted. In total, 16 epitopes (9 from MHC class I and 7 from MHC class II) were selected. Among the T-cell epitopes, MHC class I (IPFAMQMAYRFN) and MHC class II (VTLACFVLAAVYRIN) were classified as strongly antigenic. Digestion analysis verified the safety and stability of the peptides predicted during this study. Furthermore, docking analyses of predicted peptides showed significant interactions with the HLA-B7 allele.

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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.

The Rift Valley fever virus (RVFV) is a zoonotic arbovirus and pathogenic to both humans and animals. Currently, no proven effective RVFV drugs or licensed vaccine are available for human or animal use. Hence, there is an urgent need to develop effective treatment options to control this viral infection. RVFV glycoprotein N (GN), glycoprotein C (GC), and nucleocapsid (N) proteins are attractive antiviral drug targets due to their critical roles in RVFV replication. In present study, an integrated docking-based virtual screening of more than 6000 phytochemicals with known antiviral activities against these conserved RVFV proteins was conducted. The top five hit compounds, calyxin C, calyxin D, calyxin J, gericudranins A, and blepharocalyxin C displayed optimal binding against all three target proteins. Moreover, multiple parameters from the molecular dynamics (MD) simulations and MM/GBSA analysis confirmed the stability of protein–ligand complexes and revealed that these compounds may act as potential pan-inhibitors of RVFV replication. Our computational analyses may contribute toward the development of promising effective drugs against RVFV infection.