SARS-CoV-2 has caused millions of infections and more than 600,000 deaths worldwide. Despite the large number of studies to date, there is no specifically effective treatment available for SARS-CoV-2. However, it has been proposed to target reused drugs with potential antiviral activity to the interface between the angiotensin-converting enzymes 2 (ACE2) and the receptor binding domain (RBD) of SARS-CoV-2 to avoid cell recognition. Some non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to have some type of activity against a wide variety of viruses including SARS-CoV-2. Therefore, we carried out an exhaustive computational biophysical study of various NSAIDs targeting the RBD-ACE2 complex using multiple comparative analysis of docking and molecular dynamics. Only the Ibuprofen (Propionic acid derivative), Aspirin (Salicylate), and the Acetaminophen (p-aminophenol derivative) had a thermodynamically favorable docking with the interface of the RBD-ACE2 complex under the conditions of this study. Although, Ibuprofen was the NSAIDs with the most thermodynamically favorable docking in the shortest simulation time, and was the major inducer of structural changes, conformational changes, and overall changes in the complex throughout the simulation, including disturbances in composition and distribution of cavities at the interface. Results that point to Ibuprofen as an NSAID that, under the conditions outlined in this investigation, may have the highest probability of generating a disturbance in the stability of the RBD-ACE2 complex. This statement, although it could contribute information for the empirical treatment and prevention of COVID-19, represents only a theoretical orientation and approach, and requires its experimental demonstration because our predictions cannot secure a pharmacologically and clinically relevant interaction. However, these results are relevant due that suggest a possible mechanism of action of Ibuprofen against COVID-19 in addition to its anti-inflammatory properties, of which there are no reports in the literature.

SARS-CoV-2已在全球造成数百万感染，超过600,000例死亡。尽管迄今为止进行了大量研究，但没有针对SARS-CoV-2的特别有效的治疗方法。然而，已经提出将具有潜在抗病毒活性的重用药物靶向于血管紧张素转化酶2（ACE2）和SARS-CoV-2的受体结合域（RBD）之间的界面，以避免细胞识别。据报道，某些非甾体抗炎药（NSAIDs）对包括SARS-CoV-2在内的多种病毒具有某种类型的活性。因此，我们使用对接和分子动力学的多个比较分析，对靶向RBD-ACE2复合物的各种NSAID进行了详尽的计算生物物理研究。仅布洛芬（丙酸衍生物），阿司匹林（水杨酸酯），在本研究条件下，对乙酰氨基酚（对氨基苯酚衍生物）与RBD-ACE2配合物的界面具有热力学上有利的对接。尽管布洛芬是在最短的模拟时间内对热力学最有利的对接的非甾体类抗炎药，并且是整个模拟过程中结构变化，构象变化和复合物整体变化的主要诱因，包括对结构的干扰和空腔的分布。接口。指向布洛芬作为NSAID的结果，在本研究概述的条件下，可能会最有可能在RBD-ACE2复合物的稳定性中产生干扰。该声明虽然可以为COVID-19的经验治疗和预防提供信息，代表的只是理论取向和方法，并且需要进行实验证明，因为我们的预测无法确保药理和临床相关的相互作用。然而，这些结果是相关的，因为这表明除了其抗炎特性外，布洛芬还可能对COVID-19起作用，目前尚无文献报道。