The genome feature of SARS-CoV-2 leads the virus to mutate and creates new variants of concern. Tackling viral mutations is also an important challenge for the development of a new vaccine. Accordingly, in the present study, we undertook to identify B- and T-cell epitopes with immunogenic potential for eliciting responses to SARS-CoV-2, using computational approaches and its tailoring to coronavirus variants. A total of 47 novel epitopes were identified as immunogenic triggering immune responses and no toxic after investigation with in silico tools. Furthermore, we found these peptide vaccine candidates showed a significant binding affinity for MHC I and MHC II alleles in molecular docking investigations. We consider them to be promising targets for developing peptide-based vaccines against SARS-CoV-2. Subsequently, we designed two efficient multi-epitopes vaccines against the SARS-CoV-2, the first one based on potent MHC class I and class II T-cell epitopes of S (FPNITNLCPF–NYNYLYRLFR–MFVFLVLLPLVSSQC), M (MWLSYFIASF–GLMWLSYFIASFRLF), E (LTALRLCAY–LLFLAFVVFLLVTLA), and N (SPRWYFYYL–AQFAPSASAFFGMSR). The second candidate is the result of the tailoring of the first designed vaccine according to three classes of SARS-CoV-2 variants. Molecular docking showed that the protein-protein binding interactions between the vaccines construct and TLR2–TLR4 immune receptors are stable complexes. These findings confirmed that the final multi-epitope vaccine could be easily adapted to new viral variants. Our study offers a shortlist of promising epitopes that can accelerate the development of an effective and safe vaccine against the virus and its adaptation to new variants. Communicated by Ramaswamy H. Sarma

Monkeypox virus (MPV) is closely related to the smallpox virus, and previous data from Africa suggest that the smallpox vaccine (VARV) is at least 85% effective in preventing MPV. No multi-epitope vaccine has yet been developed to prevent MPV infection. In this work, we used in silico structural biology and advanced immunoinformatic strategies to design a multi-epitope subunit vaccine against MPV infection. The designed vaccine sequence is adjuvanted with CpG-ODN and includes HTL/CTL epitopes for similar proteins between vaccinia virus (VACV) that induced T-cell production in vaccinated volunteers and the first draft sequence of the MPV genome associated with the suspected outbreak in several countries, May 2022. In addition, the specific binding of the modified vaccine and the immune Toll-like receptor 9 (TLR9) was estimated by molecular interaction studies. Strong interaction in the binding groove as well as good docking scores confirmed the stringency of the modified vaccine. The stability of the interaction was confirmed by a classical molecular dynamics simulation and normal mode analysis. Then, the immune simulation also indicated the ability of this vaccine to induce an effective immune response against MPV. Codon optimization and in silico cloning of the vaccine into the pET-28a (+) vector also showed its expression potential in the E. coli K12 system. The promising data obtained from the various in silico studies indicate that this vaccine is effective against MPV. However, additional in vitro and in vivo studies are still needed to confirm its efficacy.Communicated by Ramaswamy H. Sarma.

Proteasome inhibitors have effective anti-tumor activity in cell culture and can induce apoptosis by interfering with the degradation of cell cycle proteins. 20S Proteasome is acknowledged to be a satisfactory target that has persistent properties against the human immune defense and is obligatory for the degradation of some vital proteins. This study aimed to identify potential inhibitors against 20S proteasome, specifically the β5 subunit, using structure-based virtual screening and molecular docking to reduce the number of ligands that should be eligible for experimental assays. A total of 4961 molecules with anticancer activity were screened from the ASINEX database. The filtered compounds that showed higher docking affinity were then used in more sophisticated molecular docking simulations with AutoDock Vina for validation. Finally, six drug molecules (BDE 28974746, BDE 25657353, BDE 29746159, BDD 27844484, BDE 29746109, and BDE 29746162) exhibited highly significant interactions compared to the positive controls were retained. Among these six molecules, three molecules (BDE 28974746, BDE 25657353, and BDD 27844484) showed high binding affinity and binding energy compared with Carfilzomib and Bortezomib. Molecular simulation and dynamics studies of the top three drug molecules in each case allowed us to draw further conclusions about their stability with the β5 subunit. Computed absorption, distribution, metabolism, excretion and toxicity studies on these derivatives showed encouraging results with very low toxicity, distribution, and absorption. These compounds may serve as potential hits for further biological evaluation in the development of new proteasome inhibitors.Communicated by Ramaswamy H. Sarma.