Coarse-grained molecular dynamics-guided immunoinformatics to explain the binder and non-binder classification of Cytotoxic T-cell epitope for SARS-CoV-2 peptide-based vaccine discovery.

Epitope-based peptide vaccine can elicit T-cell immunity against SARS-CoV-2 to clear the infection. However, finding the best epitope from the whole antigen is challenging. A peptide screening using immunoinformatics usually starts from MHC-binding peptide, immunogenicity, cross-reactivity with the human proteome, to toxicity analysis. This pipeline classified the peptides into three categories, i.e., strong-, weak-, and non-binder, without incorporating the structural aspect. For this reason, the molecular detail that discriminates the binders from non-binder is interesting to be investigated. In this study, five CTL epitopes against HLA-A*02:01 were identified from the coarse-grained molecular dynamics-guided immunoinformatics screening. The strong binder showed distinctive activities from the non-binder in terms of structural and energetic properties. Furthermore, the second residue from the nonameric peptide was most important in the interaction with HLA-A*02:01. By understanding the nature of MHC-peptide interaction, we hoped to improve the chance of finding the best epitope for a peptide vaccine candidate.

The Effect of Ethanol on Lipid Nanoparticle Stabilization from a Molecular Dynamics Simulation Perspective.

Lipid nanoparticles (LNPs) have emerged as a promising delivery system, particularly for genetic therapies and vaccines. LNP formation requires a specific mixture of nucleic acid in a buffered solution and lipid components in ethanol. Ethanol acts as a lipid solvent, aiding the formation of the nanoparticle's core, but its presence can also affect LNP stability. In this study, we used molecular dynamics (MD) simulations to investigate the physicochemical effect of ethanol on LNPs and gain a dynamic understanding of its impact on the overall structure and stability of LNPs. Our results demonstrate that ethanol destabilizes LNP structure over time, indicated by increased root mean square deviation (RMSD) values. Changes in the solvent-accessible surface area (SASA), electron density, and radial distribution function (RDF) also suggest that ethanol affects LNP stability. Furthermore, our H-bond profile analysis shows that ethanol penetrates the LNP earlier than water. These findings emphasize the importance of immediate ethanol removal in lipid-based systems during LNP production to ensure stability.

In vitro studies on the cytotoxicity, elastase, and tyrosinase inhibitory activities of tomato (Solanum lycopersicum Mill.) extract.

Tomatoes (Solanum lycopersicum Mill.), a common vegetable in Indonesia, contain high levels of lycopene, which is good for the body. This research further investigates the activity of polar and nonpolar fractions of tomatoes as elastase and tyrosinase inhibitory, and cytotoxic agents. The extraction procedure used is maceration, fractionation through liquid-liquid fractionation, purification of phytochemical substances is achieved through the application of thin layer chromatography. Elastase and tyrosinase inhibitory activity was analyzed using spectrophotometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxic assay. The result showed that the extract yield was 0.004%. The percentage of polar fraction from the extract was 2.58%, while the nonpolar fraction was 0.69%. The elastase inhibitory activity of polar and nonpolar fractions of tomato extract is 87.21% ± 7.57% and 73.12% ± 7.44%, respectively, The elastase inhibitory activity of polar and nonpolar fractions of tomato extract is 87.21% ± 7.57% and 73.12% ± 7.44%, respectively. The fractions had higher the anti-elastase activity than the positive control quercetin (65.97% ± 3.00%). The tyrosinase inhibitory activity of polar and nonpolar fractions of tomato extract is 23.71% ± 7.91% and 41.16% ± 5.41% (kojic acid as standard is 65.07% ± 0.86%), respectively. The IC50 of the cytotoxic assay to NIH 3T3 mouse embryonic fibroblast cells of the polar and nonpolar fraction of tomato extract is 1820.90 µg/mL and 1643.86 µg/mL, respectively.