Department of Chemistry, University of Management and Technology (UMT), C-II, Johar Town, Lahore 54770, Pakistan.
Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia.
Molecules. 2024 Mar 4;29(5):1144. doi: 10.3390/molecules29051144.
The SARS-CoV-2 virus and its mutations have affected human health globally and created significant danger for the health of people all around the world. To cure this virus, the human Angiotensin Converting Enzyme-2 (ACE2) receptor, the SARS-CoV-2 main protease (Mpro), and spike proteins were found to be likely candidates for the synthesis of novel therapeutic drug. In the past, proteins were capable of engaging in interaction with a wide variety of ligands, including both manmade and plant-derived small molecules. L., , , , and were some of the plant species that were studied for their tendency to interact with SARS-CoV-2 main protease (Mpro) in this research project (6LU7). This scenario investigates the geometry, electronic, and thermodynamic properties computationally. Assessing the intermolecular forces of phytochemicals with the targets of the SARS-CoV-2 Mpro spike protein (SP) resulted in the recognition of a compound, kaempferol, as the most potent binding ligand, -7.7 kcal mol. Kaempferol interacted with ASP-187, CYS-145, SER-144, LEU 141, MET-165, and GLU-166 residues. Through additional molecular dynamic simulations, the stability of ligand-protein interactions was assessed for 100 ns. GLU-166 remained intact with 33% contact strength with phenolic OH group. We noted a change in torsional conformation, and the molecular dynamics simulation showed a potential variation in the range from 3.36 to 7.44 against a 45-50-degree angle rotation. SAR, pharmacokinetics, and drug-likeness characteristic investigations showed that kaempferol may be the suitable candidate to serve as a model for designing and developing new anti-COVID-19 medicines.
SARS-CoV-2 病毒及其突变已在全球范围内影响人类健康，对全球人民的健康构成重大威胁。为了治愈这种病毒，人类血管紧张素转换酶 2（ACE2）受体、SARS-CoV-2 主要蛋白酶（Mpro）和刺突蛋白被认为是合成新型治疗药物的可能候选物。在过去，蛋白质能够与各种配体相互作用，包括人工和植物来源的小分子。在本研究项目（6LU7）中，研究了一些植物物种，以研究它们与 SARS-CoV-2 主要蛋白酶（Mpro）相互作用的倾向。这种情况通过计算方法研究了几何形状、电子和热力学性质。评估植物化学物质与 SARS-CoV-2 Mpro 刺突蛋白（SP）的靶标之间的分子间力，导致识别出一种化合物，山奈酚，作为最有效的结合配体，-7.7 kcal mol。山奈酚与 ASP-187、CYS-145、SER-144、LEU 141、MET-165 和 GLU-166 残基相互作用。通过额外的分子动力学模拟，评估了配体-蛋白相互作用的稳定性为 100 ns。GLU-166 保持完整，与酚羟基的接触强度为 33%。我们注意到扭转构象发生了变化，分子动力学模拟显示在 3.36 到 7.44 之间的潜在变化范围与 45-50 度的角度旋转。SAR、药代动力学和药物样特性研究表明，山奈酚可能是作为设计和开发新型抗 COVID-19 药物模型的合适候选物。
