探索治疗方案对于正在进行的由SARS-CoV-2引起的COVID-19大流行至关重要。Nirmatrelvir,这是一种针对SARS-CoV-2Mpro的有效抑制剂,显示作为抗病毒治疗的希望。此外,伊维菌素,这是一种广谱抗寄生虫药物,在实验室环境中证明了对病毒的有效性。然而,其临床意义仍有争议。使用计算方法,如分子对接和100ns分子动力学模拟,我们调查了Nirmatrelvir和伊维菌素如何与SARS-CoV-2Mpro(A)相互作用。使用密度泛函理论的计算有助于阐明孤立分子的行为,主要通过分析前沿分子轨道。我们的分析揭示了不同的结合模式:Nirmatrelvir与氨基酸形成了强烈的相互作用,如MET49、MET165、HIS41、HIS163、HIS164、PHE140、CYS145、GLU166和ASN142,显示出稳定的结合,均方根偏差(RMSD)约为2.0。另一方面,伊维菌素与THR237、THR239、LEU271、LEU272和LEU287相互作用,RMSD为1.87,表明持久的互动。两种配体都稳定了Mpro(A),伊维菌素显示出稳定性和持续的相互作用,尽管形成较少的氢键。这些发现为Nirmatrelvir和伊维菌素如何与SARS-CoV-2主要蛋白酶结合提供了详细的见解,为针对COVID-19的潜在治疗策略提供有价值的信息。
Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2.
Nirmatrelvir, which is a potent inhibitor that targets the SARS-CoV-2 Mpro, shows promise as an antiviral treatment. Additionally, Ivermectin, which is a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods, such as molecular docking and 100 ns molecular dynamics simulations, we investigated how
Nirmatrelvir and Ivermectin interacted with SARS-CoV-2 Mpro(A). Calculations using density functional theory were instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns:
Nirmatrelvir formed strong interactions with amino acids, like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding, with a root-mean-square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized Mpro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how
Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19.