论文标题
针对COVID-19的选定FDA批准的药物的分子对接和结合模式分析选定的关键蛋白质靶标：为识别与COVID-COVID-19的联合疗法的努力
Molecular docking and binding mode analysis of selected FDA approved drugs against COVID-19 selected key protein targets: An effort towards drug repurposing to identify the combination therapy to combat COVID-19
论文作者
论文摘要
Covid-19的出现严重损害了抗病毒和抗生素药物的武器库。药物发现是一个多步过程，其失败率很高，成本高，将新分子开发到临床候选者中大约需要10 - 12年。另一方面，重新利用的药物也称为新用途的旧药物，是新应用的新应用FDA批准或研究药物的吸引人的替代方法。在当前由于19日期引起的大流行状况，现有的FDA批准药物的重新利用已成为治疗的第一行。这种高度传染性疾病和急性呼吸综合征冠状病毒（SARS-COV）的病毒药物具有高核苷酸相似性。因此，许多现有的病毒靶标在结构上被期望与SARS-COV相似，并且可能会受到相同化合物的抑制。在这里，我们根据其在病毒生命周期中的重要作用选择了三种病毒键蛋白：ACE2（有助于进入人宿主），病毒非结构性蛋白RNA依赖性RNA聚合酶（RDRP）NSP12和NSP16，有助于复制和病毒潜伏期（受到免疫潜伏）。 FDA批准的药物氯喹（CQ），羟基氯喹（HCQ），Remdesivir（RDV）和Arbidol（ABD）已成为与Covid-19作对抗的有前途的药物。停靠研究背后的假设是确定这些药物的结合亲和力，并确定关键的氨基酸残基在其作用机理中起着关键作用。对接研究是通过自动售货机和在线Covid-19对接服务器进行的。需要对广泛的FDA批准药物，包括更多蛋白质靶标，分子动力学研究，体外和体内生物学评估的广泛研究，以识别针对病毒生命周期各个阶段的联合治疗。
The emergence of COVID-19 has severely compromised the arsenal of antiviral and antibiotic drugs. Drug discovery is a multistep process with a high failure rate, high cost and it takes approximately 10-12 years for the development of new molecules into the clinical candidate. On the other side, drug repurposing also called old drugs for new uses, is an attractive alternative approach for a new application of marketed FDA approved or investigational drugs. In the current pandemic situation raised due to COVID-19, repurposing of existing FDA approved drugs are emerging as the first line of the treatment. The causative viral agent of this highly contagious disease and acute respiratory syndrome coronavirus (SARS-CoV) shares high nucleotide similarity. Therefore, many existing viral targets are structurally expected to be similar to SARS-CoV and likely to be inhibited by the same compounds. Here, we selected three viral key proteins based on their vital role in viral life cycle: ACE2 (helps in entry into the human host), viral nonstructural proteins RNA-dependent RNA polymerase (RdRp) NSP12, and NSP16 which helps in replication, and viral latency (invasion from immunity). The FDA approved drugs chloroquine (CQ), hydroxychloroquine (HCQ), remdesivir (RDV) and arbidol (ABD) are emerging as promising agents to combat COVID-19. Our hypothesis behind the docking studies is to determine the binding affinities of these drugs and identify the key amino acid residues playing a key role in their mechanism of action. The docking studies were carried out through Autodock and online COVID-19 docking server. Further studies on a broad range of FDA approved drugs including few more protein targets, molecular dynamics studies, in-vitro and in-vivo biological evaluation are required to identify the combination therapy targeting various stages of the viral life cycle.
