Allam Ahmed E, Assaf Hamdy K, Hassan Heba Ali, Shimizu Kuniyoshi, Elshaier Yaseen A M M
Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University Assiut 71524 Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Universities Zone New Minia City 61111 Egypt.
RSC Adv. 2020 Aug 13;10(50):29983-29998. doi: 10.1039/d0ra05265e. eCollection 2020 Aug 10.
3'-Hydroxy-4'-methoxy-chroman-7--β-d-glucopyranoside 4 was first isolated from a natural source, together with three known compounds, the ferulic acid heptyl ester 1, naringenin 2, and 4,2',4'-trihydroxy-6'-methoxychalcone-4'--β-d-glucopyranoside 3, which were isolated from peach [ (L.) Batsch] fruits. These compounds were subjected to different virtual screening strategies in order to examine their activity to combat the COVID-19 outbreak. The study design composed of some major aspects: (a) docking with main protease (M), (b) docking with spike protein, (c) 3D shape similarity study (Rapid Overlay Chemical Similarity-ROCS) to the clinically used drugs in COVID-19 patients, and finally, (d) the rule of five and the estimated pre-ADMT properties of the separated flavonoids. Docking study with M of SARS-CoV-2 (PDB ID:6LU7, and 6Y2F) showed that compound 3, its aglycone part, and compound 4 have a strong binding mode to a protease receptor with key amino acids, especially Gln:166AA, and having a similar docking pose to co-crystalized ligands. Docking with the spike protein of SARS-CoV-2 illustrated that compounds 3 and 4 have a good binding affinity to PDB ID:6VSB through the formation of HBs with Asp:467A and Asn:422A. According to ROCS analysis, compounds 1, 3, and 4 displayed high similarities to drugs that prevent SARS-Co2 entry to the lung cells or block the inflammatory storm causing lung injury. Compounds 3 and 4 are good candidates for drug development especially because they showed predicted activity against SARS-CoV-2 through different mechanisms either by preventing genome replication or by blocking inflammatory storm that trigger lung injury. These compounds were isolated from peach fruit, and the study supports data and continues with the recommendation of peach fruits in controlling and managing COVID-19 cases.
3'-羟基-4'-甲氧基色满-7--β-d-吡喃葡萄糖苷4首次从天然来源中分离出来，同时还分离出三种已知化合物，阿魏酸庚酯1、柚皮素2和4,2',4'-三羟基-6'-甲氧基查耳酮-4'--β-d-吡喃葡萄糖苷3，它们是从桃[ (L.) Batsch]果实中分离得到的。为了研究这些化合物对抗新冠疫情爆发的活性，对它们进行了不同的虚拟筛选策略。该研究设计包括几个主要方面：(a) 与主要蛋白酶（M）对接，(b) 与刺突蛋白对接，(c) 与新冠患者临床使用药物的3D形状相似性研究（快速叠加化学相似性-ROCS），最后，(d) 分离出的黄酮类化合物的五规则和预测的ADMT前性质。对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的M进行对接研究（蛋白质数据银行编号：6LU7和6Y2F）表明，化合物3及其苷元部分以及化合物4与蛋白酶受体具有强烈的结合模式，涉及关键氨基酸，特别是Gln:166AA，并且与共结晶配体具有相似的对接姿势。与SARS-CoV-2的刺突蛋白对接表明，化合物3和4通过与Asp:467A和Asn:422A形成氢键，对蛋白质数据银行编号：6VSB具有良好的结合亲和力。根据ROCS分析，化合物1、3和4与预防SARS-CoV-2进入肺细胞或阻断导致肺损伤的炎症风暴的药物具有高度相似性。化合物3和4是药物开发的良好候选物，特别是因为它们通过不同机制显示出对SARS-CoV-2的预测活性，要么通过阻止基因组复制，要么通过阻断引发肺损伤的炎症风暴。这些化合物是从桃果实中分离出来的，该研究支持相关数据，并继续推荐桃果实在控制和管理新冠病例方面的作用。
