Siddiqa M A, Rao D S, Suvarna G, Chennamachetty V K, Verma M K, Rao M V R
Department of Biotechnological, Acharya Nagarjuna University, Guntur, Andhra Pradesh India.
Department of Biotechnology, Yogi Vemana University, Kadapa, Andhra Pradesh India.
Int J Pept Res Ther. 2021;27(3):1633-1640. doi: 10.1007/s10989-021-10196-x. Epub 2021 Mar 17.
The realm Riboviria constitutes Coronaviruses, which led to the emergence of the pandemic COVID 19 in the twenty-first century affected millions of lives. At present, the management of COVID 19 largely depends on antiviral therapeutics along with the anti-inflammatory drug. The vaccine is under the final clinical phase, and emergency use is available. We aim at ACE2 and Nsp10/Nsp16 MTase as potential drug candidate in COVID 19 management in the present work. For drug designing, various computational simulation strategies have been employed like Swiss-Model, Hawk Dock, HDOCK, py Dock, and PockDrug for homology modeling, binding energies of the molecule with a target, simulate the conformation and binding poses, statistics of protein lock with target key and drug ability, respectively. The current in-silico screening depicts that the spike protein receptor is complementary to the target when bound to each other and forms a stable complex. The MMGBSA free energy binding property of receptor and ligand is critical. The intermolecular Statistics with the target Nsp10/Nsp16 MTase complex are plausible. We have also observed a high-affinity pocket binding site with the target. Therefore, the favorable intermolecular interactions and Physico-chemical properties emanate as a drug candidate treating COVID-19. This study has approached computational tools to analyze the conformation, binding affinity, and drug ability of receptor-ligand. Thus, the spike receptor with its ACE2 receptor with Nsp10/Nsp16 MTase complex would be a potent drug against SARS CoV-2 and can cure the infection as per consensus scoring.
核糖病毒域包含冠状病毒，其导致了21世纪大流行的新冠病毒肺炎出现，影响了数百万人的生命。目前，新冠病毒肺炎的治疗很大程度上依赖于抗病毒疗法以及抗炎药物。疫苗正处于最终临床阶段，且已可供紧急使用。在本研究中，我们将血管紧张素转换酶2（ACE2）和Nsp10/Nsp16甲基转移酶作为新冠病毒肺炎治疗的潜在候选药物。对于药物设计，我们采用了多种计算模拟策略，如瑞士模型、鹰对接、高清对接、py对接和口袋药物，分别用于同源建模、分子与靶点的结合能计算、模拟构象和结合姿势、蛋白质与靶点关键部位的锁定统计以及药物能力统计。当前的计算机模拟筛选表明，刺突蛋白受体与靶点结合时相互互补并形成稳定复合物。受体和配体的MMGBSA自由能结合特性至关重要。与靶点Nsp10/Nsp16甲基转移酶复合物的分子间统计是合理的。我们还观察到与靶点有一个高亲和力的口袋结合位点。因此，有利的分子间相互作用和物理化学性质使其成为治疗新冠病毒肺炎的候选药物。本研究运用计算工具分析了受体-配体的构象、结合亲和力和药物能力。因此，具有ACE2受体的刺突受体与Nsp10/Nsp16甲基转移酶复合物将是一种对抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的有效药物，并且根据共识评分可以治愈感染。
