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Antiviral lead compounds from marine sponges.

Sagar S, Kaur M, Minneman KP - Mar Drugs (2010)

Bottom Line: Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment.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.

View Article: PubMed Central - PubMed

Affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Jeddah, Saudi Arabia. sunil.sagar@kaust.edu.sa

ABSTRACT
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.

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Structures of mycalamide A and B.
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f2-marinedrugs-08-02619: Structures of mycalamide A and B.

Mentions: Perry et al. [28] first reported the isolation and in vitro antiviral activity of mycalamide A and mycalamide B (Figure 2) from a New Zealand sponge of the genus Mycale in 1988 and 1990, respectively. The crude extract containing 2% mycalamide A was found to be active against A59 corona virus. After treatment with crude extract at 0.1 mg/kg, mice infected with virus survived for 14 days, however the mice infected with virus died within eight days. Mycalamide A also inhibited the Herpes simplex type I and Polio type I viruses at a concentration of 5 ng/disc. Mycalamide B was found to be more potent than mycalamide A, which was active at a concentration of 1–2 ng/disc [29]. Examining the mechanisms involved in the actions of these compounds, Burres and Clement discovered the inhibition of protein synthesis and translation of RNA into protein in a cell-free lysate of rabbit reticulocytes [30]. A new study also described the binding of mycalamide A to the E site of the large ribosomal subunit of Haloarcula marismortui and inhibition of protein synthesis [31]. This property of protein synthesis inhibition may be attributed to their biological activity as antiviral agents.


Antiviral lead compounds from marine sponges.

Sagar S, Kaur M, Minneman KP - Mar Drugs (2010)

Structures of mycalamide A and B.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2992996&req=5

f2-marinedrugs-08-02619: Structures of mycalamide A and B.
Mentions: Perry et al. [28] first reported the isolation and in vitro antiviral activity of mycalamide A and mycalamide B (Figure 2) from a New Zealand sponge of the genus Mycale in 1988 and 1990, respectively. The crude extract containing 2% mycalamide A was found to be active against A59 corona virus. After treatment with crude extract at 0.1 mg/kg, mice infected with virus survived for 14 days, however the mice infected with virus died within eight days. Mycalamide A also inhibited the Herpes simplex type I and Polio type I viruses at a concentration of 5 ng/disc. Mycalamide B was found to be more potent than mycalamide A, which was active at a concentration of 1–2 ng/disc [29]. Examining the mechanisms involved in the actions of these compounds, Burres and Clement discovered the inhibition of protein synthesis and translation of RNA into protein in a cell-free lysate of rabbit reticulocytes [30]. A new study also described the binding of mycalamide A to the E site of the large ribosomal subunit of Haloarcula marismortui and inhibition of protein synthesis [31]. This property of protein synthesis inhibition may be attributed to their biological activity as antiviral agents.

Bottom Line: Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment.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.

View Article: PubMed Central - PubMed

Affiliation: Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900, Jeddah, Saudi Arabia. sunil.sagar@kaust.edu.sa

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus