Abstract

Recently Chloroquine and its derivative Hydroxychloroquine have garnered enormous interest amongst the clinicians and health authorities’ world over as a potential treatment to contain COVID-19 pandemic. The present research aims at investigating the therapeutic potential of Chloroquine and its potent derivative Hydroxychloroquine against SARS-CoV-2 viral proteins. At the same time screening was performed for some chemically synthesized derivatives of Chloroquine and compared their binding efficacy with chemically synthesized Chloroquine derivatives through in silico approaches. For the purpose of the study, some essential viral proteins and enzymes were selected that are implicated in SARS-CoV-2 replication and multiplication as putative drug targets. Chloroquine, Hydroxychloroquine, and some of their chemically synthesized derivatives, taken from earlier published studies were selected as drug molecules. We have conducted molecular docking and related studies between Chloroquine and its derivatives and SARS-CoV-2 viral proteins, and the findings show that both Chloroquine and Hydroxychloroquine can bind to specific structural and non-structural proteins implicated in the pathogenesis of SARS-CoV-2 infection with different efficiencies. Our current study also shows that some of the chemically synthesized Chloroquine derivatives can also potentially inhibit various SARS-CoV-2 viral proteins by binding to them and concomitantly effectively disrupting the active site of these proteins. These findings bring into light another possible mechanism of action of Chloroquine and Hydroxychloroquine and also pave the way for further drug repurposing and remodeling.

Communicated by Ramaswamy H. Sarma

摘要

最近，氯喹及其衍生物羟氯喹作为遏制 COVID-19 大流行的潜在治疗方法，引起了全世界临床医生和卫生当局的极大兴趣。本研究旨在研究氯喹及其有效衍生物羟氯喹对抗 SARS-CoV-2 病毒蛋白的治疗潜力。同时对一些化学合成的氯喹衍生物进行了筛选，并通过计算机模拟方法比较了它们与化学合成的氯喹衍生物的结合效力。出于研究目的，选择了一些与 SARS-CoV-2 复制和增殖有关的重要病毒蛋白和酶作为假定的药物靶点。取自早期发表的研究的氯喹、羟氯喹及其一些化学合成衍生物被选为药物分子。我们对氯喹及其衍生物与SARS-CoV-2病毒蛋白进行了分子对接及相关研究，结果表明氯喹和羟氯喹均可与SARS-CoV发病机制中涉及的特定结构和非结构蛋白结合。 2.感染效率不同。我们目前的研究还表明，一些化学合成的氯喹衍生物还可以通过与各种 SARS-CoV-2 病毒蛋白结合并同时有效破坏这些蛋白的活性位点来潜在地抑制这些蛋白。这些发现揭示了氯喹和羟氯喹的另一种可能的作用机制，也为进一步的药物重新利用和重塑铺平了道路。

拉马斯瓦米·萨尔马 (Ramaswamy H. Sarma) 通讯