基于 SARS-CoV-2 病毒感染的主蛋白酶 3CL 对 6,6-二甲基-3-氮杂双环[3.1.0]己烷-2-甲酰胺衍生物的计算机识别与分子动力学模拟

In silico identification and molecular dynamic simulations of derivatives of 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide against main protease 3CL of SARS-CoV-2 viral infection.

机构信息

Department of Physics, School of Physical & Decision Science, Babasaheb Bhimrao Ambedkar University, Lucknow, 226025, Uttar Pradesh, India.

出版信息

J Mol Model. 2023 Apr 5;29(5):130. doi: 10.1007/s00894-023-05535-2.

CONTEXT

The unavailability of target-specific antiviral drugs for SARS-CoV-2 viral infection kindled the motivation to virtually design derivatives of 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide as potential antiviral inhibitors against the concerned virus. The molecular docking and molecular dynamic results revealed that the reported derivatives have a potential to act as antiviral drug against SARS-CoV-2. The reported hit compounds can be considered for in vitro and in vivo analyses.

METHODS

Fragment-based drug designing was used to model the derivatives. Furthermore, DFT simulations were carried out using B3LYP/6-311G** basis set. Docking simulations were performed by using a combination of empirical free energy force field with a Lamarckian genetic algorithm under AutoDock 4.2. By the application of AMBER14 force field and SPCE water model, molecular dynamic simulations and MM-PBSA were calculated for 100 ns.

背景

由于针对 SARS-CoV-2 病毒感染的靶向抗病毒药物无法获得，因此激发了人们设计 6,6-二甲基-3-氮杂双环[3.1.0]己烷-2-甲酰胺衍生物作为潜在抗病毒抑制剂来对抗相关病毒的动机。分子对接和分子动力学研究结果表明，所报道的衍生物具有作为抗 SARS-CoV-2 抗病毒药物的潜力。所报道的命中化合物可考虑进行体外和体内分析。

方法

使用片段基药物设计来构建衍生物。此外，使用 B3LYP/6-311G**基组进行 DFT 模拟。通过使用经验自由能力场与 Lamarckian 遗传算法相结合的方式，在 AutoDock 4.2 中进行对接模拟。通过应用 AMBER14 力场和 SPCE 水模型，计算了 100ns 的分子动力学模拟和 MM-PBSA。