Abstract

The novel coronavirus (SARS-CoV-2) causes severe acute respiratory syndrome and can be fatal. In particular, antiviral drugs that are currently available to treat infection in the respiratory tract have been experienced, but there is a need for new antiviral drugs that are targeted and inhibit coronavirus. The antiviral properties of organic compounds found in nature, especially coumarins, are known and widely studied. Coumarins, which are also metabolites in many medicinal drugs, should be investigated as inhibitors against coronavirus due to their pharmacophore properties (low toxicity and high pharmacokinetic properties). The easy addition of substituents to the chemical structures of coumarins makes these structures unique for the drug design. This study focuses on factors that increase the molecular binding and antiviral properties of coumarins. Molecular docking studies have been carried out to five different proteins (Spike S1-subunit, NSP5, NSP12, NSP15, and NSP16) of the SARS-CoV-2 and two proteins (ACE2 and VKORC1) of human. The best binding scores for 17 coumarins were determined for NSP12 (NonStructural Protein-12). The highest score (–10.01 kcal/mol) in the coumarin group is 2-morpholinoethan-1-amine substituted coumarin. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analyses of selected ligand-protein complexes were performed. The binding energies in each 5 ns were calculated and it was found that the interaction between ligand and target protein were stable.

Communicated by Ramaswamy H. Sarma

摘要

新型冠状病毒 (SARS-CoV-2) 会导致严重的急性呼吸系统综合症，并可能致命。尤其是目前可用于治疗呼吸道感染的抗病毒药物已经出现，但需要新的靶向并抑制冠状病毒的抗病毒药物。自然界中发现的有机化合物（尤其是香豆素）的抗病毒特性是已知的并被广泛研究。香豆素也是许多药物中的代谢物，由于其药效团特性（低毒性和高药代动力学特性），应将其作为冠状病毒的抑制剂进行研究。在香豆素的化学结构中轻松添加取代基使得这些结构对于药物设计来说是独一无二的。本研究重点关注增加香豆素分子结合和抗病毒特性的因素。已经对 SARS-CoV-2 的五种不同蛋白质（Spike S1 亚基、NSP5、NSP12、NSP15 和 NSP16）和人类的两种蛋白质（ACE2 和 VKORC1）进行了分子对接研究。NSP12（NonStructural Protein-12）确定了 17 种香豆素的最佳结合分数。香豆素组中的最高分数 (–10.01 kcal/mol) 是 2-morpholinoethan-1-amine 取代的香豆素。对选定的配体-蛋白质复合物进行分子力学泊松-玻尔兹曼表面积 (MM-PBSA) 分析。计算每5ns的结合能，发现配体与靶蛋白的相互作用是稳定的。SARS-CoV-2 的 NSP12、NSP15 和 NSP16）和人类的两种蛋白质（ACE2 和 VKORC1）。NSP12（NonStructural Protein-12）确定了 17 种香豆素的最佳结合分数。香豆素组中的最高分数 (–10.01 kcal/mol) 是 2-morpholinoethan-1-amine 取代的香豆素。对选定的配体-蛋白质复合物进行分子力学泊松-玻尔兹曼表面积 (MM-PBSA) 分析。计算每5ns的结合能，发现配体与靶蛋白的相互作用是稳定的。SARS-CoV-2 的 NSP12、NSP15 和 NSP16）和人类的两种蛋白质（ACE2 和 VKORC1）。NSP12（NonStructural Protein-12）确定了 17 种香豆素的最佳结合分数。香豆素组中的最高分数 (–10.01 kcal/mol) 是 2-morpholinoethan-1-amine 取代的香豆素。对选定的配体-蛋白质复合物进行分子力学泊松-玻尔兹曼表面积 (MM-PBSA) 分析。计算每5ns的结合能，发现配体与靶蛋白的相互作用是稳定的。对选定的配体-蛋白质复合物进行分子力学泊松-玻尔兹曼表面积 (MM-PBSA) 分析。计算每5ns的结合能，发现配体与靶蛋白的相互作用是稳定的。对选定的配体-蛋白质复合物进行分子力学泊松-玻尔兹曼表面积 (MM-PBSA) 分析。计算每5ns的结合能，发现配体与靶蛋白的相互作用是稳定的。

由 Ramaswamy H. Sarma 传达