Bajad Nilesh Gajanan, Rayala Swetha, Gutti Gopichand, Sharma Anjali, Singh Meenakshi, Kumar Ashok, Singh Sushil Kumar
Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India.
Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
Curr Res Pharmacol Drug Discov. 2021;2:100026. doi: 10.1016/j.crphar.2021.100026. Epub 2021 May 14.
The outbreak of existing public health distress is threatening the entire world with emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel coronavirus disease 2019 (COVID-19) is mild in most people. However, in some elderly people with co-morbid conditions, it may progress to pneumonia, acute respiratory distress syndrome (ARDS) and multi organ dysfunction leading to death. COVID-19 has caused global panic in the healthcare sector and has become one of the biggest threats to the global economy. Drug discovery researchers are expected to contribute rapidly than ever before. The complete genome sequence of coronavirus had been reported barely a month after the identification of first patient. Potential drug targets to combat and treat the coronavirus infection have also been explored. The iterative structure-based drug design (SBDD) approach could significantly contribute towards the discovery of new drug like molecules for the treatment of COVID-19. The existing antivirals and experiences gained from SARS and MERS outbreaks may pave way for identification of potential drug molecules using the approach. SBDD has gained momentum as the essential tool for faster and costeffective lead discovery of antivirals in the past. The discovery of FDA approved human immunodeficiency virus type 1 (HIV-1) inhibitors represent the foremost success of SBDD. This systematic review provides an overview of the novel coronavirus, its pathology of replication, role of structure based drug design, available drug targets and recent advances in in-silico drug discovery for the prevention of COVID-19. SARSCoV- 2 main protease, RNA dependent RNA polymerase (RdRp) and spike (S) protein are the potential targets, which are currently explored for the drug development.
现有公共卫生危机的爆发，正随着严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的出现和迅速传播而威胁着整个世界。2019年新型冠状病毒病（COVID-19）在大多数人身上症状较轻。然而，在一些患有合并症的老年人中，它可能会发展为肺炎、急性呼吸窘迫综合征（ARDS）和多器官功能障碍，导致死亡。COVID-19在医疗保健领域引起了全球恐慌，并已成为全球经济面临的最大威胁之一。药物研发研究人员预计要比以往更快地做出贡献。首例患者确诊后仅一个月，冠状病毒的完整基因组序列就已公布。对抗和治疗冠状病毒感染的潜在药物靶点也已得到探索。基于结构的迭代药物设计（SBDD）方法可显著有助于发现用于治疗COVID-19的新型药物样分子。现有的抗病毒药物以及从SARS和MERS疫情中获得的经验，可能为使用该方法鉴定潜在药物分子铺平道路。过去，SBDD已成为快速且经济高效地发现抗病毒药物先导物的重要工具。FDA批准的人类免疫缺陷病毒1型（HIV-1）抑制剂的发现代表了SBDD的首要成功。本系统综述概述了新型冠状病毒、其复制病理学、基于结构的药物设计的作用、可用的药物靶点以及用于预防COVID-19的计算机辅助药物发现的最新进展。SARS-CoV-2主要蛋白酶、RNA依赖性RNA聚合酶（RdRp）和刺突（S）蛋白是潜在靶点，目前正针对这些靶点进行药物研发探索。
