Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity, Medicinal Chemistry and Natural Products (LR11ES39), Faculty of Sciences of Monastir, University of Monastir, Monastir 5000, Tunisia.
Department of Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle, Germany.
Molecules. 2022 Aug 19;27(16):5303. doi: 10.3390/molecules27165303.
In addition to vaccines, antiviral drugs are essential in order to suppress COVID-19. Although some inhibitor candidates have been determined to target the SARS-CoV-2 protein, there is still an urgent need to continue researching novel inhibitors of the SARS-CoV-2 main protease 'Omicron P132H', a protein that has recently been discovered. In the present study, in the search for therapeutic alternatives to treat COVID-19 and its recent variants, we conducted a structure-based virtual screening using docking studies for a new series of pyrazolo[3,4-]pyrimidin-4(5)-one derivatives -, which were synthesized from the condensation reaction of pyrazolopyrimidinone-hydrazide () with a series of electrophiles. Some significant ADMET predictions-in addition to the docking results-were obtained based on the types of interactions formed and the binding energy values were compared to the reference anti- SARS-CoV-2 redocked drug nirmatrelvir.
除了疫苗，抗病毒药物也是抑制 COVID-19 的关键。虽然已经确定了一些抑制剂候选物来针对 SARS-CoV-2 蛋白，但仍然迫切需要继续研究 SARS-CoV-2 主蛋白酶“Omicron P132H”的新型抑制剂，这是一种最近发现的蛋白。在本研究中，为了寻找治疗 COVID-19 及其最近变种的替代方法，我们进行了基于结构的虚拟筛选，使用对接研究了一系列新的吡唑并[3,4-]嘧啶-4(5)-酮衍生物，这些衍生物是通过吡唑并嘧啶酮-酰肼（）与一系列亲电试剂的缩合反应合成的。除了对接结果之外，根据形成的相互作用类型还获得了一些显著的 ADMET 预测，并且将结合能值与参考抗 SARS-CoV-2 再对接药物 nirmatrelvir 进行了比较。
