Hamoda Alshaimaa M, Fayed Bahgat, Ashmawy Naglaa S, El-Shorbagi Abdel-Nasser A, Hamdy Rania, Soliman Sameh S M
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Front Pharmacol. 2021 May 13;12:666664. doi: 10.3389/fphar.2021.666664. eCollection 2021.
The current pandemic caused by SARS-CoV2 and named COVID-19 urgent the need for novel lead antiviral drugs. Recently, United States Food and Drug Administration (FDA) approved the use of remdesivir as anti-SARS-CoV-2. Remdesivir is a natural product-inspired nucleoside analogue with significant broad-spectrum antiviral activity. Nucleosides analogues from marine sponge including spongouridine and spongothymidine have been used as lead for the evolutionary synthesis of various antiviral drugs such as vidarabine and cytarabine. Furthermore, the marine sponge is a rich source of compounds with unique activities. Marine sponge produces classes of compounds that can inhibit the viral cysteine protease (M) such as esculetin and ilimaquinone and human serine protease (TMPRSS2) such as pseudotheonamide C and D and aeruginosin 98B. Additionally, sponge-derived compounds such as dihydrogracilin A and avarol showed immunomodulatory activity that can target the cytokines storm. Here, we reviewed the potential use of sponge-derived compounds as promising therapeutics against SARS-CoV-2. Despite the reported antiviral activity of isolated marine metabolites, structural modifications showed the importance in targeting and efficacy. On that basis, we are proposing a novel structure with bifunctional scaffolds and dual pharmacophores that can be superiorly employed in SARS-CoV-2 infection.
由严重急性呼吸综合征冠状病毒2（SARS-CoV2）引起并命名为COVID-19的当前大流行凸显了对新型先导抗病毒药物的迫切需求。最近，美国食品药品监督管理局（FDA）批准使用瑞德西韦治疗SARS-CoV-2感染。瑞德西韦是一种受天然产物启发的核苷类似物，具有显著的广谱抗病毒活性。来自海洋海绵的核苷类似物，包括海绵尿苷和海绵胸苷，已被用作多种抗病毒药物（如阿糖腺苷和阿糖胞苷）进化合成的先导物。此外，海洋海绵是具有独特活性的化合物的丰富来源。海洋海绵产生的几类化合物可以抑制病毒半胱氨酸蛋白酶（M），如七叶亭和异香豆素，以及人类丝氨酸蛋白酶（TMPRSS2），如拟神酰胺C和D以及铜绿假单胞菌素98B。此外，海绵衍生的化合物，如二氢格拉西林A和阿伐他汀，显示出可以靶向细胞因子风暴的免疫调节活性。在此，我们综述了海绵衍生化合物作为抗SARS-CoV-2的有前景治疗药物的潜在用途。尽管已报道分离出的海洋代谢产物具有抗病毒活性，但结构修饰显示出在靶向性和疗效方面的重要性。在此基础上，我们提出了一种具有双功能支架和双药效团的新型结构，可更有效地用于SARS-CoV-2感染的治疗。
