COVID-19 outbreak poses a severe health emergency to the global community. Due to availability of limited data, the selection of an effective treatment is a challenge. Hydroxychloroquine (HCQ), a chloroquine (CQ) derivative administered for malaria and autoimmune diseases, has been shown to be effective against both Severe Acute Respiratory Syndrome (SARS-CoV-1) and SARS-CoV-2. Apart from the known adverse effects of these drugs, recently the use of CQ and HCQ as a potential treatment for COVID-19 is under flux globally. In this study, we focused on identifying a more potent analogue of HCQ and CQ against the spike protein of SAR-CoV-2 that can act as an effective antiviral agent for COVID-19 treatment. Systematic pharmacokinetics, drug-likeness, basicity predictions, virtual screening and molecular dynamics analysis (200 ns) were carried out to predict the inhibition potential of the analogous compounds on the spike protein. This work identifies the six potential analogues, out of which two compounds, namely 1-[1-(6-Chloroquinolin-4-yl) piperidin-4-yl]piperidin-3-ol and (1R,2R)-2-N-(7-Chloroquinolin-4-yl)cyclohexane-1,2-diamine interact with the active site of the spike protein similar to HCQ and CQ respectively with augmented safety profile.

COVID-19 的爆发给国际社会带来了严重的卫生紧急情况。由于数据有限，选择有效的治疗方法是一项挑战。羟氯喹 (HCQ) 是一种用于治疗疟疾和自身免疫性疾病的氯喹 (CQ) 衍生物，已被证明对严重急性呼吸系统综合症 (SARS-CoV-1) 和 SARS-CoV-2 均有效。除了这些药物已知的副作用外，最近全球范围内使用 CQ 和 HCQ 作为 COVID-19 的潜在治疗方法正在发生变化。在这项研究中，我们专注于确定一种更有效的 HCQ 和 CQ 类似物来对抗 SAR-CoV-2 的刺突蛋白，它可以作为 COVID-19 治疗的有效抗病毒剂。系统药代动力学、药物相似性、碱度预测、进行了虚拟筛选和分子动力学分析（200 ns）以预测类似化合物对刺突蛋白的抑制潜力。这项工作确定了六种潜在的类似物，其中有两种化合物，即 1-[1-(6-Chloroquinolin-4-yl) piperidin-4-yl]piperidin-3-ol 和 (1R,2R)-2-N -(7-Chloroquinolin-4-yl)cyclohexane-1,2-diamine 与刺突蛋白的活性位点相互作用，分别类似于 HCQ 和 CQ，具有增强的安全性。