Department of Biochemistry, Era's Lucknow Medical College and Hospital, Era University, Lucknow, UP, India.
Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Lucknow, UP, India.
J Biomol Struct Dyn. 2022 Aug;40(12):5515-5546. doi: 10.1080/07391102.2021.1871863. Epub 2021 Feb 1.
A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. PASS analysis of morin reference antiviral drugs baricitinib, remdesivir and hydroxychloroquine revealed that morin displayed no violations of Lipinski's rule of five and other druglikeness filters. Morin also displayed no tumorigenic, reproductive or irritant effects and exhibited good absorption and permeation through GI (clogP <5). In principal component analysis, morin appeared closest to baricitinib in 3D space. Morin displayed potent binding to spike glycoprotein, main protease 3CLPro and papain-like protease PLPro of SARS-CoV-2, SARS-CoV and MERS-CoV using molecular docking and significant binding to three viral-specific host proteins human ACE2, importin-α and poly (ADP-ribose) polymerase (PARP)-1, further lending support to its antiviral efficacy. Additionally, morin displayed potent binding to pro-inflammatory cytokines IL-6, 8 and 10 also supporting its anti-inflammatory activity. MD simulation of morin with SARS-CoV-2 3CLPro and PLPro displayed strong stability at 300 K. Both complexes exhibited constant RMSDs of protein side chains and Cα atoms throughout the simulation run time. In conclusion, morin might hold considerable therapeutic potential for the treatment and management of not only COVID-19, but also SARS and MERS if studied further. Communicated by Ramaswamy H. Sarma.
2019 年，一种新型冠状病毒 SARS-CoV-2 的突然爆发，现已成为一种威胁人类生存的大流行病。由于目前尚无有效的适当疫苗来对抗这种新出现的病原体，因此需要寻找新的治疗和预防资源分子。为此，本研究评估了存在于水果、蔬菜和各种草药中的黄酮醇桑色素的抗病毒潜力。对桑色素与参考抗病毒药物巴利昔替尼、瑞德西韦和羟氯喹的 PASS 分析表明，桑色素不违反 Lipinski 的五规则和其他类药性过滤器。桑色素也没有表现出致瘤、生殖或刺激性作用，并且通过 GI（clogP<5）显示出良好的吸收和渗透。在主成分分析中，桑色素在 3D 空间中与巴利昔替尼最为接近。桑色素与 SARS-CoV-2、SARS-CoV 和 MERS-CoV 的刺突糖蛋白、主要蛋白酶 3CLPro 和木瓜样蛋白酶 PLPro 显示出强大的结合能力，使用分子对接，并与三种病毒特异性宿主蛋白 人 ACE2、importin-α 和多聚（ADP-核糖）聚合酶（PARP）-1 显著结合，进一步支持其抗病毒功效。此外，桑色素还与促炎细胞因子 IL-6、8 和 10 显示出强大的结合能力，支持其抗炎活性。用 SARS-CoV-2 3CLPro 和 PLPro 进行的 MD 模拟显示，桑色素在 300 K 时具有很强的稳定性。在整个模拟运行时间内，两个复合物的蛋白质侧链和 Cα 原子都表现出恒定的 RMSD。总之，如果进一步研究，桑色素可能对治疗和管理 COVID-19 以及 SARS 和 MERS 具有相当大的治疗潜力。Ramaswamy H. Sarma 通讯。
