Background: Due to the constant mutation of virus and the lack of specific therapeutic drugs, the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still poses a huge threat to the health of people, especially those with underlying diseases. Therefore, drug discovery against the SARS-CoV-2 remains of great significance.Methods: With the main protease of virus as the inhibitor target, 9,614 genistein derivatives were virtually screened by LeDock and AutoDock Vina, and the top 20 compounds with highest normalized scores were obtained. Molecular dynamics simulations were carried out for studying interactions between these 20 compounds and the target protein. The drug-like properties, activity, and ADMET of these compounds were also evaluated by DruLiTo software or online server.Results: Twenty compounds, including compound 11, were screened by normalized molecular docking, which could bind to the target through multiple non-bonding interactions. Molecular dynamics simulation results showed that compounds 2, 4, 5, 11, 13, 14, 17, and 18 had the best binding force with the target protein of SARS-CoV-2, and the absolute values of binding free energies all exceeded 50 kJ/mol. The drug-likeness properties indicated that a variety of compounds including compound 11 were worthy of further study. The results of bioactivity score prediction found that compounds 11 and 12 had high inhibitory activities against protease, which indicated that these two compounds had the potential to be further developed as COVID-19 inhibitors. Finally, compound 11 showed excellent predictive ADMET properties including high absorption and low toxicity.Conclusion: These in silico work results show that the preferred compound 11 (ZINC000111282222), which exhibited strong binding to SARS-CoV-2 main protease, acceptable drug-like properties, protease inhibitory activity and ADMET properties, has great promise for further research as a potential therapeutic agent against COVID-19.
Modern trams have been widely used around the world, especially in China. This paper explores the main influencing factors of modern trams’ passenger flow at the early operational stage. The system dynamics model is adopted for dealing with the problem on hand. Tram Line 1 in Huai’an, Jiangsu Province, China is selected as the case study. Data are collected using the RP and SP survey. The sensitivity test and extreme condition test are performed. The simulation results demonstrate that four variables (i.e., land development intensity, fares, service level, and transfer efficiency) significantly affect passenger flow. Land development intensity is the most significant factor, and the effect of service level on passenger flow is higher than that of the fares. The departure interval of 10 minutes is the maximum psychological limit that passengers can bear, and 2 RMB is a reasonable price. Such conclusions can provide guidance for the planning and design of modern trams and address the problem of shortage of passengers at an early stage.
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