The outbreak of respiratory disease, COVID-19 caused by SARS-CoV-2 has now been spread globally and the number of new infections is rising every moment. There are no specific medications that are currently available to combat the disease. The spike receptor of SARS-CoV-2 facilitates the viral entry into a host cell and initiation of infection. Targeting the viral entry at the initial stage has a better advantage than inhibiting it in later stages of the viral life cycle. This study deals with identification of the potential natural molecule or its derivatives from MolPort Databank as SARS-CoV-2 spike receptor inhibitors using structure-based virtual screening followed by molecular dynamics simulation. On the basis of ADME properties, docking score, MMGBSAbinding energy, 150 ns molecular docking studies, and final molecular dynamics analysis, two natural compounds – 3 (MolPort-002-535-004) docking score –9.10 kcal mol-1 and 4 (MolPort-005-910-183) docking score –8.5 kcal mol^-1, are selected as potential in-silico spike receptor inhibitors. Both hits are commercially available and can be further used for in-vitro and in-vivo studies. Findings of this study can facilitate rational drug design against SARS-CoV-2 spike receptor.

由SARS-CoV-2引起的呼吸道疾病COVID-19的爆发现已在全球蔓延，新感染人数每时每刻都在上升。目前没有专门的药物可以对抗这种疾病。SARS-CoV-2 的刺突受体有助于病毒进入宿主细胞并引发感染。在病毒生命周期的初始阶段针对病毒进入比在病毒生命周期的后期阶段抑制它具有更好的优势。本研究利用基于结构的虚拟筛选和分子动力学模拟，从 MolPort 数据库中鉴定潜在的天然分子或其衍生物作为 SARS-CoV-2 刺突受体抑制剂。根据 ADME 性质、对接分数、MMGBSA 结合能、150 ns 分子对接研究和最终分子动力学分析，两种天然化合物 – 3 (MolPort - 002-535-004) 对接分数 –9.10 kcal mol-1 和4 ( MolPort-005-910-183) 对接分数 –8.5 kcal mol ^-1，被选为潜在的计算机内尖峰受体抑制剂。这两种产品均可商业化购买，并可进一步用于体外和体内研究。这项研究的结果可以促进针对 SARS-CoV-2 刺突受体的合理药物设计。