Abstract

This research investigates antiviral potential of extracted honeybee products against COVID-19 main protease (Mpro) by computational methods. The crystal structure of COVID-19 Mpro was obtained from the protein data bank. Six synthetic drugs with antiviral properties were used as control samples in order to compare the results with those of natural ligands. The six honeybee components, namely 3,4,5-Tricaffeoylquinic acid, Kaempferol-3-O-glucoside, (E)-2′-Geranyl-3′,4′,7-Trihydroxyflavanone, 6-Cinnamylchrysin, (+)-Pinoresinol, and (24E)-3-Oxo-27,28-dihydroxycycloart-24-en-26-oic acid, have represented the lowest binding energies of −9.0, −8.5, −8.2, −7.8, −7.7, −7.3 and −6.7 Kcal/mol, respectively. These natural inhibitors were then picked for further investigations on their pharmacokinetic features. Also a 150 ns of Molecular dynamics simulations were carried out in order to evaluate their effects on protein structure and dynamics. The 3, 4, 5-Tricaffeoylquinic acid is hopefully proposed for COVID-19 Mpro inhibition if further in vitro, in vivo, and clinical trial studies will approve its effectiveness against COVID-19.

摘要

本研究通过计算方法研究提取的蜜蜂产品对 COVID-19 主要蛋白酶 (Mpro) 的抗病毒潜力。COVID-19 Mpro 的晶体结构来自蛋白质数据库。六种具有抗病毒特性的合成药物被用作对照样品，以便将结果与天然配体的结果进行比较。蜜蜂的六种成分，即3,4,5-三咖啡酰奎宁酸、山奈酚-3- O-葡萄糖苷、(E)-2'-Geranyl-3',4',7-Trihydroxyflavanone、6-Cinnamylchrysin、(+)-Pinoresinol 和 (24E)-3-Oxo-27,28-dihydroxycycloart-24-en -26-oic acid 的结合能最低，分别为 -9.0、-8.5、-8.2、-7.8、-7.7、-7.3 和 -6.7 Kcal/mol。然后挑选这些天然抑制剂以进一步研究它们的药代动力学特征。还进行了 150 ns 的分子动力学模拟，以评估它们对蛋白质结构和动力学的影响。如果进一步的体外、体内和临床试验研究将证明其对 COVID-19 的有效性，3, 4, 5-三咖啡酰奎宁酸有望被提议用于 COVID-19 Mpro 抑制。