使用1,5-二取代四唑-1,2,3-三唑的杂交衍生物处理严重急性呼吸系统综合征冠状病毒2型主要蛋白酶:一种计算机分析

C. Cortés-García, L. Chacón-García, Jorge Emmanuel Mejía-Benavides, E. Díaz-Cervantes
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引用次数: 16

摘要

考虑到全球突发公共卫生事件的实际情况,并根据目前抑制SARS-CoV-2治疗covid - 19的方法的最新进展,我们通过对上述病毒主要蛋白酶(CoV-2-MPro)的硅质测定,对先前合成的1,5-二取代四唑-1,2,3-三唑家族进行了评估。结果表明,其中三种化合物与所选靶标的相互作用比共结晶分子更有利,共结晶分子是肽样衍生物。研究还发现,疏水相互作用在配体-靶分子偶联中也起着关键作用,因为疏水表面进入活性位点较高。最后,基于以下结果提出了药效团模型,并采用与本工作相同的方法设计和测试了一系列1,5- dt衍生物。综上所述,以isatin为取代基(P8)的化合物具有较高的配体-靶标相互作用,可抑制CoV-2-MProprotein,是抗covid - 19的强候选药物。
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Tackling the SARS-CoV-2 main protease using hybrid derivatives of 1,5-disubstituted tetrazole-1,2,3-triazoles: an in silico assay
In regard to the actual public health global emergency and, based on the state of the art about the ways to inhibit the SARS-CoV-2 treating the COVID19, a family of 1,5-disubstituted tetrazole-1,2,3-triazoles, previously synthesized, have been evaluated through in silico assays against the main protease of the mentioned virus (CoV-2-MPro). The results show that three of these compounds present a more favorable interaction with the selected target than the co-crystallized molecule, which is a peptide-like derivative. It was also found that also hydrophobic interactions play a key role in the ligand-target molecular couplings, due to the higher hydrophobic surfaces into the active site. Finally, a pharmacophore model has been proposed based on the results below, and a family of 1,5-DT derivatives has been designed and tested with the same methods employed in this work. It was concluded that the compound with the isatin as a substituent (P8) present the higher ligand-target interaction, which makes this a strong drug candidate against COVID19, due can inhibit the CoV-2-MProprotein.
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