Department of Chemistry, University of Sargodha, Sargodha, Pakistan.
J Biomol Struct Dyn. 2021 Aug;39(12):4243-4255. doi: 10.1080/07391102.2020.1775703. Epub 2020 Jul 6.
Recent outbreak of novel Coronavirus disease () pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and its N terminal domain (NTD) of Nucleocapsid protein (N protein) binds to the viral (+) sense RNA and results in virus ribonucleoprotien complex, essential for the virus replication. The N protein is composed of a serine-rich linker region sandwiched between NTD and C terminal (CTD). These terminals play a role in viral entry and its processing post entry. The NTD of SARS-CoV-2 N protein forms orthorhombic crystals and binds to the viral genome. Therefore, there is always a quest to target RNA binding domain of nucleocapsid phosphoprotein (NTD-N-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for is still under debate globally because of some side effects associated with it. This study involves the interactions of Chloroquine and Hydroxychloroquine with the NTD-N-protein of SARS-CoV-2. With the help of various computational methods, we have explored the potential role of both of these antiviral drugs for the treatment of patients by comparing the efficacy of both of the drugs to bind to NTD-N-protein. In our research Hydroxychloroquine exhibited potential inhibitory effects of NTD-N-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for trials of Hydroxychloroquine for the patients infected with . Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with . We further hypothesize that the comparative NTD-N-protein -drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine.Communicated by Ramaswamy H. Sarma.
最近在全球范围内爆发的新型冠状病毒疾病（COVID-19）大流行与严重急性呼吸系统综合症有关。与该大流行相关的死亡人数每天都在增加。SARS-CoV-2 是一种包膜病毒，其核衣壳蛋白（N 蛋白）的 N 端结构域（NTD）与病毒（+） sense RNA 结合，导致病毒核糖核蛋白复合物的形成，这对于病毒复制是必不可少的。N 蛋白由富含丝氨酸的连接区夹在 NTD 和 C 端（CTD）之间组成。这些末端在病毒进入及其进入后的加工中起作用。SARS-CoV-2 N 蛋白的 NTD 形成正交晶体并与病毒基因组结合。因此，人们一直在寻找靶向核衣壳磷蛋白（NTD-N-蛋白的 RNA 结合域，这反过来可能有助于控制人类由 SARS-CoV-2 引起的疾病。氯喹和羟氯喹作为潜在治疗方法的作用仍在全球范围内引起争议，因为它们存在一些副作用。这项研究涉及氯喹和羟氯喹与 SARS-CoV-2 的 NTD-N-蛋白的相互作用。借助各种计算方法，我们通过比较两种药物与 NTD-N-蛋白结合的功效，探索了这两种抗病毒药物治疗患者的潜在作用。在我们的研究中，羟氯喹对 NTD-N-蛋白的抑制作用比氯喹（-6.30 kcal/mol）更强，其结合能为-7.28 kcal/mol，在 SARS-CoV-2 受体识别易感细胞时。这项研究的结果强烈呼吁对感染 COVID-19 的患者进行羟氯喹试验。此外，只要未被诊断出患有 COVID-19，建议的羟氯喹剂量可能会降低与冠状病毒患者接触或直接提供护理的医护人员感染的机会。我们进一步假设，比较 NTD-N-蛋白 - 药物对接相互作用可以帮助理解其他候选重新定位药物的比较疗效，直到发现适当的疫苗。通讯作者为 Ramaswamy H. Sarma。
