Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Jeddah, Saudi Arabia.
Mar Drugs. 2010 Oct 11;8(10):2619-38. doi: 10.3390/md8102619.
Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hoped to be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed.
海洋海绵是目前海洋环境中发现的具有药理活性化合物的最丰富来源之一。这些生物活性分子通常是次生代谢产物,其主要功能是使细胞间的通讯和防御得以实现和/或调节。它们通常由海绵中的功能酶簇和/或其相关共生微生物产生。从海绵中提取的天然产物先导化合物通常被发现是有前途的药物制剂。其中一些已成功获批用于临床的抗病毒药物,或已进入临床试验的后期阶段。这些药物大多用于治疗人类免疫缺陷病毒(HIV)和单纯疱疹病毒(HSV)。到目前为止,报道的最重要的海洋来源抗病毒先导化合物是从海绵 Tethya crypta 中分离出的核苷 Ara-A(阿昔洛韦)。它抑制疱疹、水痘和带状疱疹病毒的病毒 DNA 聚合酶和 DNA 合成。然而,由于新类型病毒的发现和耐药株的出现,需要不断开发新的抗病毒先导化合物。本文综述了几种有望开发成未来药物的海绵来源抗病毒先导化合物。在临床试验期间,作为药物开发,供应问题通常是这些化合物的主要瓶颈。然而,宏基因组学和高通量微生物培养领域的进展提高了这些技术可以实现此类化合物具有成本效益的大规模生产的可能性。本文还讨论了生物技术方法在海洋药物开发方面的前景。