Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Bioprocess Engineering Division, Smykon Biotech Pvt LtD, Nagercoil, Kanyakumari, Tamil Nadu 629201, India.
J Infect Public Health. 2023 May;16(5):784-791. doi: 10.1016/j.jiph.2023.03.004. Epub 2023 Mar 7.
Monkeypox virus (mpox) disease is caused by a double-stranded DNA virus from the Poxviridae family. The mpox virus showed structural similarity with smallpox virus disease. The recent outbreak of mpox infection in the rest of African countries causes public health issues of increased pandemic potential. Mpox virus is involved in the viral replication cycle through the biocatalytic reaction of precursor polyproteins cleavage.
The main objective of the study was to analyze the molecular interactions between mpox and FDA-approved drugs.
The primary and secondary structure of the protein was retrieved and FDA approved drug was screened using AutoDock. The best hit was analyzed and the molecular interactions were studied. Model validation analyzes the peptide, energy of hydrogen bonds, steric conflicts and bond planarity. Z-score was calculated using ProSA-web tool and the score tested the native fold from other alternative folds.
The confidence level of the submitted amino acids was> 80 % and the maximum confidence score for a single template was 98.2 %. The generated proteinase model was subjected to analyze the distribution of atoms and the using ERRAT server. The overall quality score was 88.535 and this value represents the amino acid percentage with anticipated error value and the value falling below the rejection limit. The Z-score of this study result was within the Z-score range (-4.17) validated for native enzymes. The binding pockets of the enzyme were determined in this study and two binding pockets were predicted using the automatic online tool using the web server. The selected FDA-approved drugs were ordered based on their minimum binding energy to the proteinase.
Molecular docking studies revealed the involvement of various hydrophobic interactions between FDA-approved drugs and amino acid residues of monkeypox virus proteinase.
猴痘病毒（mpox）疾病是由痘病毒科的双链 DNA 病毒引起的。mpox 病毒与天花病毒疾病表现出结构相似性。最近在非洲其他国家爆发的 mpox 感染引起了公众对大流行潜力增加的健康问题的关注。mpox 病毒通过前体多蛋白切割的生物催化反应参与病毒复制周期。
本研究的主要目的是分析 mpox 与美国食品和药物管理局批准药物之间的分子相互作用。
使用 AutoDock 检索蛋白质的一级和二级结构，并筛选美国食品和药物管理局批准的药物。分析最佳命中并研究分子相互作用。模型验证分析肽、氢键能量、立体冲突和键平面性。使用 ProSA-web 工具计算 Z 分数，并测试分数以从其他替代折叠中测试天然折叠。
提交氨基酸的置信水平>80%，单个模板的最大置信得分为 98.2%。生成的蛋白酶模型用于分析原子分布和使用 ERRAT 服务器。整体质量评分为 88.535，该值代表具有预期误差值的氨基酸百分比和低于拒绝限制的值。本研究结果的 Z 分数在为天然酶验证的-4.17 的 Z 分数范围内。本研究确定了酶的结合口袋，并使用自动在线工具使用 Web 服务器预测了两个结合口袋。根据与蛋白酶的最低结合能对选定的美国食品和药物管理局批准的药物进行排序。
分子对接研究揭示了美国食品和药物管理局批准的药物与猴痘病毒蛋白酶的氨基酸残基之间存在各种疏水相互作用。
