Lopinavir; A Potent Drug against Coronavirus Infection: Insight from Molecular Docking Study
Lopinavir; A Potent Drug against Coronavirus Infection: Insight from Molecular Docking Study
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DOI：
10.5812/archcid.13823
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发表时间：
2017-10-01
影响因子：
1.4
通讯作者：
Dayer, Mohammad Saaid
中科院分区：
文献类型：
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作者：
Dayer, Mohammad Reza;Taleb-Gassabi, Sara;Dayer, Mohammad Saaid
背景：严重急性呼吸综合征（SARS）是一种危及生命的病毒感染，由包膜冠状病毒家族的阳性单链RNA病毒引起。这种疾病与发烧、咳嗽和呼吸道并发症相关，导致全球 15% 以上的死亡率。到目前为止，除了支持治疗外，没有任何治疗方法。然而，主要病毒蛋白酶最近被认为是抗 SARS 感染药物设计的合适靶点，因为它在冠状病毒繁殖所需的多蛋白加工中发挥着重要作用。 目的：本计算机研究旨在评估美国 FDA 批准临床应用的抗 HIV-1 蛋白酶抑制剂对 SARS 蛋白酶抑制的效果。 方法：在本研究中，采用对接和分子动力学实验来检查抑制剂在相似 pH、温度和生理条件下对冠状病毒蛋白酶的影响。水溶液中的压力。整个工作过程中使用Hex软件5.1版和GROMACS 4.5.5进行对接分析。结果：计算出的RMSD、RMSF、MSD、偶极矩、扩散系数、结合能和结合位点相似性等参数表明抑制剂与SARS蛋白酶有效结合，导致其结构发生变化，这与蛋白酶抑制相符。结论：HIV 1蛋白酶抑制剂对克罗病毒蛋白酶的抑制效力如下：LPV > RTV > APV > TPV > SQV。洛匹那韦和沙奎那韦分别是克罗诺病毒蛋白酶最强和最弱的抑制剂。
Background: The severe acute respiratory syndrome (SARS) is a life threatening viral infection caused by a positive, single stranded RNA virus from the enveloped coronaviruse family. Associated with fever, cough, and respiratory complications, the illness causes more than 15% mortality worldwide. So far, there is no remedy for the illness except supportive treatments. However, the main viral proteinase has recently been regarded as a suitable target for drug design against SARS infection due to its vital role in polyproteins processing necessary for coronavirus reproduction.Objectives: The present in silico study was designed to evaluate the effects of anti HIV-1 proteases inhibitors, approved for clinical applications by US FDA, on SARS proteinase inhibition.Methods: In the present study, docking and molecular dynamic experiments were applied to examine the effect of inhibitors on coronavirus proteinase under physiological conditions of similar pH, temperature, and pressure in aqueous solution. Hex software version 5.1 and GROMACS 4.5.5 were used for docking analysis throughout this work.Results: The calculated parameters such as RMSD, RMSF, MSD, dipole moment, diffusion coefficient, binding energy, and binding site similarity indicated effective binding of inhibitors to SARS proteinase resulting in their structural changes, which coincide with proteinase inhibition.Conclusions: The inhibitory potency of HIV 1 protease inhibitors to cronovirus proteinase was as follows: LPV > RTV > APV > TPV > SQV. Lopinavir and Saquinavir were the most and the least powerful inhibitors of cronovirus proteinase, respectively.