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Overexpression of polo-like kinase 1 (PLK1) has been found in many different types of cancers. With its essential role in cell proliferation, PLK1 has been determined to be a broad-spectrum anti-cancer target. In this study, 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations were applied on a series of novel pteridinone derivatives as PLK1 inhibitors to discover anti-cancer drug candidates. In this work, three models—CoMFA (Q² = 0.67, R² = 0.992), CoMSIA/SHE (Q² = 0.69, R² = 0.974), and CoMSIA/SEAH (Q² = 0.66, R² = 0.975)—of pteridinone derivatives were established. The three models that were established gave Rpred2 = 0.683, Rpred 2= 0.758, and Rpred 2= 0.767, respectively. Thus, the predictive abilities of the three proposed models were successfully evaluated. The relations between the different champs and activities were well-demonstrated by the contour chart of the CoMFA and CoMSIA/SEAH models. The results of molecular docking indicated that residues R136, R57, Y133, L69, L82, and Y139 were the active sites of the PLK1 protein (PDB code: 2RKU), in which the more active ligands can inhibit the enzyme of PLK1. The results of the molecular dynamic MD simulation diagram were obtained to reinforce the previous molecular docking results, which showed that both inhibitors remained stable in the active sites of the PLK1 protein (PDB code: 2RKU) for 50 ns. Finally, a check of the ADME-Tox properties of the two most active molecules showed that molecular N° 28 could represent a good drug candidate for the therapy of prostate cancer diseases.

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A novel, human-infecting coronavirus causing COVID-19 was first identified in Wuhan, China in December 2019. Within a short span of time the virus recorded more than 1 million deaths, worldwide. This study addresses the overall evolutionary process from complete genomes of COVID-19. Addressing the complexity of the task, network-based approaches were used in mapping samples to their reported locations. A total of 473 complete human coronavirus genomes from 20 different countries were studied, including samples from 17 states of the United States and samples from the Cruise-Diamond Princess. The phylodynamic network of a global scale was classified into five clusters containing two clusters of the samples from the USA. Cluster B was a shared cluster of samples from China and the USA, while clusters A and C were of a diverse nature. Chinese samples aggregated in clusters A and B which aided in retaining the homogeneous viral genomic pool. In contrast, samples from the USA and Spain were split into distinct clusters which indicated multiple port entries and a possibility of implying a delay in quarantine measures. In the intra-USA samples, we found that sequences reported from Washington and Virginia were scattered indicating evolutionary diversity. This report provides an insight into the transmission pattern of CoV2, which is complicated to evaluate exclusively through the conventional surveillance means.