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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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Structure of Ara-A.
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f1-marinedrugs-08-02619: Structure of Ara-A.

Mentions: In 1950, Bergmann et al. [6] isolated from the Caribbean sponge Tethya crypta (Tethylidae) the nucleosides spongothymidine and spongouridine, which contained an arabinose sugar rather than the more common ribose sugar found in these nucleosides. Vidarabine or Ara-A is a synthetic analogue of spongouridine with improved antiviral activity. The antiviral activity of adenine arabinoside (vidarabine, Ara-A, Figure 1) was first described by Privat de Garilhe and De Rudder in 1964 [10]. The work of Whitley in 1976 further confirmed the clinical usefulness of the compound in the treatment of herpes encephalitis and the other herpes infections that occasionally occur in newborns [11]. It was the first nucleoside antiviral to be licensed for the treatment of systematic herpes virus infection and one of the three marine-derived drugs currently approved by the FDA in the United States [12], however the marketing of the drug has been discontinued because the availability of newer and better antiviral agents on the market.


Antiviral lead compounds from marine sponges.

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

Structure of Ara-A.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-marinedrugs-08-02619: Structure of Ara-A.
Mentions: In 1950, Bergmann et al. [6] isolated from the Caribbean sponge Tethya crypta (Tethylidae) the nucleosides spongothymidine and spongouridine, which contained an arabinose sugar rather than the more common ribose sugar found in these nucleosides. Vidarabine or Ara-A is a synthetic analogue of spongouridine with improved antiviral activity. The antiviral activity of adenine arabinoside (vidarabine, Ara-A, Figure 1) was first described by Privat de Garilhe and De Rudder in 1964 [10]. The work of Whitley in 1976 further confirmed the clinical usefulness of the compound in the treatment of herpes encephalitis and the other herpes infections that occasionally occur in newborns [11]. It was the first nucleoside antiviral to be licensed for the treatment of systematic herpes virus infection and one of the three marine-derived drugs currently approved by the FDA in the United States [12], however the marketing of the drug has been discontinued because the availability of newer and better antiviral agents on the market.

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