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Emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants have raised concerns about the efficacy of vaccines. The present study aimed to compare the potential of Delta and Omicron variant-specific mRNA vaccines in inducing immune responses. B cell and T cell epitopes and population coverage of spike (S) glycoprotein of the variants were predicted using the Immune Epitope Database. The molecular docking was carried out between the protein and different toll-like receptors, as well as the receptor-binding domain (RBD) protein and angiotensin-converting-enzyme 2 (ACE2) cellular receptor using ClusPro. The molecular simulation was done for each docked RBD-ACE2 using YASARA. The mRNA secondary structure was predicted through the RNAfold. The simulation of immune responses to the mRNA vaccine construct was performed using C-ImmSim. Apart from a few positions, no significant difference was observed in the prediction of S protein B cell and T cell epitopes of these two variants. The lower amounts of Median consensus percentile in the Delta variant in similar positions signify its stronger affinity to major histocompatibility complex (MHC) II binding alleles. Docking of Delta S protein with TLR3, TLR4, and TLR7 and also its RBD with ACE2 showed striking interactions with the lower binding energy than Omicron. In the immune simulation, elevated levels of cytotoxic T lymphocytes, helper T lymphocytes, and memory cells in both the active and resting states and the main regulators of the immune system suggested the capacity of mRNA constructs to elicit robust immune responses against SARS-CoV-2 variants. Considering slight differences in the binding affinity to MHC II binding alleles, activation of TLRs, mRNA secondary structure stability, and concentration of immunoglobulins and cytokines, the Delta variant is suggested for the mRNA vaccine construction. Further studies are being done to prove the efficiency of the design construct. [ABSTRACT FROM AUTHOR]

Background and purpose: Cancer is the leading cause of death in today's world, therefore the efforts to achieve anticancer drugs with higher potency and fewer side effects have always been conducted by researchers in the field of pharmaceutical chemistry. Monastrol, a cytotoxic small molecule, from dihydropyrimidinone scaffold, is an inhibitor of the kinesin-5 protein. So, efforts to identify more derivatives of this molecule have been of interest. Experimental approach: Some of monastrol's analogs as Eg5 inhibitors with different substitution patterns were analyzed, synthesized, and their cytotoxic effects were evaluated on MCF-7 and HeLa cancerous cells in vitro using the MTT assay. The structure-activity relationship (SAR) was studied in silico by molecular docking. Findings / Results: Among all proposed structures, in ducking study, those with hydrophobic moieties on the C2-N3 region, those with a hydroxyl group on the phenyl on C4 position, and those with a carboxylic group on C5 were the best candidates. In vitro studies, on the other side, emphasized that monastrol still was the most potent derivative. Another finding was the more moderate activity of synthesized compounds on the HeLa cell compared to the MCF-7 cell line. During different challenges for substitution at 5-position, some earlier reports around the dihydropyrimidinone reactions were questioned. It seems that the change at the position 5 is not merely accessible, as earlier reports claimed. Also, we could not achieve any better cell cytotoxicity by the larger group in the thiourea region or position 5; nonetheless, it seems that the introduction of a methylene group at this position could be beneficial. Conclusion and implications: The initial results of this study were valuable in terms of design and synthesis and will be useful for future investigations. [ABSTRACT FROM AUTHOR]