Abstract：
The novel coronavirus disease 2019 (Covid-19) outburst is still threatening global health. This highly contagious viral disease is caused by the infection of SARS-CoV-2 virus. Covid-19 and post-Covid-19 complications induce noteworthy mortality. Potential chemical hits and leads against SARS-CoV-2 for combating Covid-19 are urgently required. In the present study, a virtual-screening protocol was executed on potential Amaryllidaceae alkaloids from a pool of natural compound library against SARS-CoV-2 main protease (Mpro) and transmembrane serine protease (TMPRSS2). For the collected 1016 alkaloids from the curated library, initially, molecular docking using AutoDock Vina (ADV), and thereafter 100 ns molecular-dynamic (MD) simulation has been executed for the best top-ranked binding affinity compounds for both the viral and host proteins. Comprehensive intermolecular-binding interactions profile of Amaryllidaceae alkaloids suggested that phyto-compounds Galantamine, Lycorenine, and Neronine as potent modulators of SARS-CoV-2 Mpro and host TMPRSS2 protein. All atomistic long range 100 ns MD simulation studies of each top ranked complex in triplicates also illustrated strong binding affinity of three compounds towards Mpro and TMPRSS2. Identified compounds might be recommended as prospective anti-viral agents for future drug development selectively targeting the SARS-CoV-2 Mpro or blocking host TMPRSS2 receptor, subjected to pre-clinical and clinical assessment for a better understanding of in-vitro molecular interaction and in-vivo validation.Communicated by Ramaswamy H. Sarma.
摘要：
2019年新型冠状病毒病（Covid-19）爆发仍在威胁全球健康。这种高度传染性的病毒性疾病是由SARS-CoV-2病毒感染引起的。Covid-19和Covid-19后并发症导致显著的死亡率。迫切需要针对SARS-CoV-2的潜在化学打击和线索，以对抗Covid-19。在本研究中,对来自针对SARS-CoV-2主蛋白酶(Mpro)和跨膜丝氨酸蛋白酶(TMPRSS2)的天然化合物库的潜在石豆科生物碱进行了虚拟筛选.对于从精选文库中收集的1016种生物碱，最初,使用AutoDockVina(ADV)进行分子对接，此后，对病毒和宿主蛋白的最佳顶级结合亲和力化合物进行了100ns分子动力学（MD）模拟。石豆科生物碱的综合分子间结合相互作用谱表明，植物化合物加兰他敏，Lycorinine,和Neronine作为SARS-CoV-2Mpro和宿主TMPRSS2蛋白的有效调节剂。每个最高等级的复合物的所有原子长距离100nsMD模拟研究一式三份也显示了三种化合物对Mpro和TMPRSS2的强结合亲和力。鉴定的化合物可能被推荐作为未来药物开发的前瞻性抗病毒药物，选择性靶向SARS-CoV-2Mpro或阻断宿主TMPRSS2受体。进行临床前和临床评估，以更好地了解体外分子相互作用和体内验证。由RamaswamyH.Sarma沟通。
