Table1_Marine Sponge is a Promising Natural Source of Anti-SARS-CoV-2 Scaffold.DOCX

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 (Mpro) 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.

当前由SARS-CoV2引发并命名为COVID-19的疫情，迫切需要开发新型抗病毒药物。近期，美国食品药品监督管理局（FDA）批准了瑞德西韦作为抗SARS-CoV-2的药物使用。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。海洋海绵中的核苷类似物，包括海绵鸟嘌呤和海绵胸腺嘧啶，已被用作合成各种抗病毒药物（如维甲苷和阿糖胞苷）的先导化合物。此外，海洋海绵是富含具有独特活性的化合物的宝库。海洋海绵产生能够抑制病毒半胱氨酸蛋白酶（Mpro）如香豆素和依罗奎酮以及人类丝氨酸蛋白酶（TMPRSS2）如伪紫杉碱C和D及铜绿素98B等化合物的类别。此外，海绵衍生的化合物如二氢格拉齐林A和avarol显示出免疫调节活性，可靶向细胞因子风暴。在此，我们回顾了海绵衍生物作为对抗SARS-CoV-2的有前景治疗药物的潜在应用。尽管报道了分离的海洋代谢物的抗病毒活性，结构修饰显示了靶向和效力的意义。基于此，我们提出了一种新型结构，具有双功能骨架和双重药效基团，这种结构在SARS-CoV-2感染中可能具有优越的应用价值。