RESUMO
Humans around the globe have been severely affected by SARS-CoV-2 and no treatment has yet been authorized for the treatment of this severe condition brought by COVID-19. Here, an in silico research was executed to elucidate the inhibitory potential of selected thiazolides derivatives against SARS-CoV-2 Protease (Mpro) and Methyltransferase (MTase). Based on the analysis; 4 compounds were discovered to have efficacious and remarkable results against the proteins of the interest. Primarily, results obtained through this study not only allude these compounds as potential inhibitors but also pave the way for in vivo and in vitro validation of these compounds.
RESUMO
DNA replication is one of the specific processes to be considered in all the living organisms, specifically eukaryotes. The prevalence of DNA replication is significant for an evolutionary transition at the beginning of life. DNA replication proteins are those proteins which support the process of replication and are also reported to be important in drug design and discovery. This information depicts that DNA replication proteins have a very important role in human bodies, however, to study their mechanism, their identification is necessary. Thus, it is a very important task but, in any case, an experimental identification is time-consuming, highly-costly and laborious. To cope with this issue, a computational methodology is required for prediction of these proteins, however, no prior method exists. This study comprehends the construction of novel prediction model to serve the proposed purpose. The prediction model is developed based on the artificial neural network by integrating the position relative features and sequence statistical moments in PseAAC for training neural networks. Highest overall accuracy has been achieved through tenfold cross-validation and Jackknife testing that was computed to be 96.22% and 98.56%, respectively. Our astonishing experimental results demonstrated that the proposed predictor surpass the existing models that can be served as a time and cost-effective stratagem for designing novel drugs to strike the contemporary bacterial infection.
RESUMO
Beta-adrenergic stimulation of the heart results in an enhanced relaxation rate in association with phosphorylation of both cardiac troponin I (cTnI) and phospholamban (PLB). We studied new lines of mice generated by crossbreeding mice that express slow skeletal troponin I (ssTnI) with PLB knockout (PLBKO) mice. This crossbreeding resulted in the generation of PLB/cTnI, PLB/ssTnI, PLBKO/cTnI, and PLBKO/ssTnI mice. Perfusion with isoproterenol (ISO) significantly increased the peak amplitude of fura-2 ratio in PLB/cTnI, PLBKO/cTnI, and PLBKO/ssTnI groups of mice. However, in the presence of ISO, there were no differences in the peak amplitude of fura-2 ratio among cells isolated from hearts of PLB/cTnI, PLBKO/cTnI, and PLBKO/ssTnI mice. In cells from PLB/cTnI mice, the extent of shortening was increased and the time of relaxation was significantly decreased during beta-adrenergic stimulation. In PLBKO/cTnI cells, stimulation with ISO resulted in an increased extent of shortening and no change in time of relaxation. However, stimulation with ISO in cells isolated from PLBKO/ssTnI mice not only significantly increased the extent of cell shortening but also increased the time of relaxation. We also determined the kinetics of relaxation of papillary muscles isolated from all four groups of animals in the presence and absence of ISO. Perfusion with ISO increased the rate of relaxation only in PLB/cTnI, PLB/ssTnI, and PLBKO/cTnI muscles. During ISO stimulation, the time of relaxation was unchanged in PLBKO/ssTnI muscles. Our data directly demonstrate that phosphorylation of both PLB and cTnI contributes to increased rate of relaxation during beta-adrenergic stimulation.