Agricultural and Food Engineering Department, Indian Institute of Technology, Kharagpur, India.
Department of Chemistry, Indian Institute of Technology, Kharagpur, India.
J Biomol Struct Dyn. 2022;40(23):12917-12931. doi: 10.1080/07391102.2021.1979427. Epub 2021 Sep 27.
Pomegranate peel, the waste product generated from pomegranate fruit, has prophylactic properties, such as antimicrobial, anti-malarial, and controls respiratory infections and influenza. Based on the previous literature and need of the hour, molecular docking was performed to evaluate the inhibitory effects of major pomegranate peel polyphenols against COVID-19. Among the 44 studied compounds, 37 polyphenols show interaction with the catalytic dyad of the M protease and 18 polyphenols have a higher binding affinity than that of the M protease inhibitor (N3), indicating their high probability of binding at ACE2: SARS-CoV-2 interface. Furthermore, several polyphenols studied in this work are found to have higher binding affinity as compared to those of hydroxychloroquine, lopinavir, nelfinavir, and curcumin, some of which have been earlier tested against COVID-19. Further, molecular dynamics simulations (200 ns) for M-polyphenols including pelargonidin3-glucoside, quercetin3-O-rhamnoside, cyanidin3-glucoside and punicalin revealed highly stable complexes with less conformational fluctuations and similar degree of compactness. Estimation of total number of intermolecular hydrogen bonds and binding free energy confirmed the stability of these M-polyphenol complexes over M-curcumin complex. Based on the greater binding affinity of polyphenols of pomegranate peel towards M as compared to that of curcumin, pomegranate peel may be considered in any herbal medicinal formulation or may be incorporated into daily diets for prevention of COVID-19.Communicated by Ramaswamy H. Sarma.
石榴皮是石榴果实的废弃物，具有预防作用，如抗菌、抗疟疾，并能控制呼吸道感染和流感。基于以往的文献和当前的需求，进行了分子对接，以评估主要石榴皮多酚对 COVID-19 的抑制作用。在所研究的 44 种化合物中，有 37 种多酚与 M 蛋白酶的催化二联体相互作用，有 18 种多酚的结合亲和力高于 M 蛋白酶抑制剂（N3），这表明它们在 ACE2：SARS-CoV-2 界面结合的可能性很高。此外，在这项工作中研究的几种多酚被发现比羟氯喹、洛匹那韦、奈非那韦和姜黄素具有更高的结合亲和力，其中一些已经在早期用于对抗 COVID-19。此外，对包括pelargonidin3-glucoside、quercetin3-O-rhamnoside、cyanidin3-glucoside 和 punicalin 在内的 M-多酚进行的分子动力学模拟（200ns）表明，它们与 M 的复合物非常稳定，构象波动较小，紧凑程度相似。估计分子间氢键的总数和结合自由能证实了这些 M-多酚复合物比 M-姜黄素复合物更稳定。基于石榴皮多酚对 M 的结合亲和力大于姜黄素，石榴皮可能被考虑用于任何草药配方中，或可纳入日常饮食以预防 COVID-19。由 Ramaswamy H. Sarma 交流。
