State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China; School of Mechanical Engineering and Automation, Northeast University, Shenyang, China.
College of Resources and Environmental Sciences, China Agricultural University, Beijing, China.
Environ Int. 2021 Feb;147:106361. doi: 10.1016/j.envint.2020.106361. Epub 2020 Dec 23.
Corona virus disease 2019 has spread worldwide, and appropriate drug design and screening activities are required to overcome the associated pandemic. Using computational simulation, blockade mechanism of SARS-CoV-2 spike receptor binding domain (S RBD) and human angiotensin converting enzyme 2 (hACE2) was clarified based on interactions between RBD and hesperidin. Interactions between anti-SARS-CoV-2 drugs and therapy were investigated based on the binding energy and druggability of the compounds, and they exhibited negative correlations; the compounds were classified into eight common types of structures with highest activity. An anti-SARS-CoV-2 drug screening strategy based on blocking S RBD/hACE2 binding was established according to the first key change (interactions between hesperidin and S RBD/hACE2) vs the second key change (interactions between anti-SARS-CoV-2 drugs and RBD/hACE2) trends. Our findings provide valuable information on the mechanism of RBD/hACE2 binding and on the associated screening strategies for anti-SARS-CoV-2 drugs based on blocking mechanisms of pockets.
新型冠状病毒病已在全球范围内传播，需要进行适当的药物设计和筛选活动，以克服相关的大流行。通过计算模拟，基于 RBD 与橙皮苷之间的相互作用，阐明了 SARS-CoV-2 刺突受体结合域 (S RBD) 和人血管紧张素转换酶 2 (hACE2) 的阻断机制。基于化合物的结合能和可药性，研究了抗 SARS-CoV-2 药物与治疗之间的相互作用，它们呈负相关；这些化合物分为八种常见的高活性结构类型。根据第一个关键变化（橙皮苷与 S RBD/hACE2 的相互作用）与第二个关键变化（抗 SARS-CoV-2 药物与 RBD/hACE2 的相互作用）趋势，建立了一种基于阻断 S RBD/hACE2 结合的抗 SARS-CoV-2 药物筛选策略。我们的研究结果为 RBD/hACE2 结合的机制以及基于口袋阻断机制的抗 SARS-CoV-2 药物相关筛选策略提供了有价值的信息。
