Background: COVID-19 emerged in late 2019 and became a pandemic disease with severe mortality and morbidity. No specific remedy exists at present, but some drugs, such as Dexamethasone, have shown clinical benefits against the causative agent, the SARS-CoV-2 virus.

Objective: To analyze the binding affinity between drugs and an SARS-CoV-2 protein through geometrical methods and to study the theoretical effectiveness of Dexamethasone as a potential treatment for COVID-19.

Methods: The binding affinity of Dexamethasone to the target SARS-CoV-2 protein was compared with those of different inhibitors. Drug molecules were docked to the SARS-CoV-2 main protease, and the system was simulated by molecular dynamics, allowing alpha shape analysis to extract geometrical features, such as the matching rates of atoms, solid angles, and the distances between atoms at interfaces. Binding affinities between drugs and the main protease were assessed by these geometrical data and the free energy of binding.

Results: The behaviour of Dexamethasone was similar to other inhibitors. The efficacy of Dexamethasone as a treatment may be due to it being a glucocorticoid and its properties as a potent inhibitor.

Conclusion: This study revealed the mechanism of action of Dexamethasone and provided a geometrical method to distinguish among potential drugs for the treatment of COVID-19.

背景：COVID-19 于 2019 年底出现，并成为具有严重死亡率和发病率的大流行病。目前尚无具体的治疗方法，但地塞米松等一些药物已显示出对病原体 SARS-CoV-2 病毒的临床益处。

目的：通过几何方法分析药物与 SARS-CoV-2 蛋白之间的结合亲和力，并研究地塞米松作为 COVID-19 潜在治疗方法的理论有效性。

方法：将地塞米松与靶标 SARS-CoV-2 蛋白的结合亲和力与不同抑制剂的结合亲和力进行比较。药物分子与SARS-CoV-2主蛋白酶对接，通过分子动力学模拟系统，通过α形状分析提取几何特征，如原子匹配率、立体角、界面原子间距等. 通过这些几何数据和结合自由能评估药物和主要蛋白酶之间的结合亲和力。

结果：地塞米松的作用与其他抑制剂相似。地塞米松作为治疗的功效可能是由于它是一种糖皮质激素及其作为有效抑制剂的特性。

结论：这项研究揭示了地塞米松的作用机制，并提供了一种几何方法来区分治疗 COVID-19 的潜在药物。