Antiviral Lead Compounds from Marine Sponges

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 hopedto 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.

Antiviral drug discovery: broad-spectrum drugs from nature

“…Two recent reviews describe the biological activities, including antiviral properties, of several compounds isolated from marine organisms 265,266 . Here we refer briefly to compounds with BSAs derived from marine sponges (reviewed in 239 ), and to squalamine, a compound isolated from the dogfish shark 85 .…”

“…Of note, the first antiviral drug approved by the FDA, the nucleoside Ara-A (Vidarabine), was isolated from a marine sponge 239 . Mycalamide A and B (24), two natural products isolated from Mycale sponges, have shown antiviral activities against coronaviruses 240 , HSV and Polio virus 268 .…”

Secondary Metabolites from Marine Sources: Review

“…Günümüze kadar 500 sünger türünden 5.000 farklı sekonder metabolit izole edilmiştir. [13][14][15] Süngerler, savunma amaçlı olarak avcıları uzaklaştırmak ve işgalci türlerle yaşam alanı için yarışabilmek, iletişim ve enfeksiyonlardan korunmak amacıyla toksik ve/veya koruyucu özelliklere sahip maddeler üretmektedir. 16,17 Süngerlerden izole edilen bu sekonder metabolitler antioksidan, antiviral, antimikrobiyal, antikanser, antidiyabetik ve "anti-fouling" (kirliliğe/paslanmaya karşı) gibi çeşitli aktivitelere sahiptirler.…”

The marine biodiscovery pipeline and ocean medicines of tomorrow

“…Vidarabine or Ara-A is a synthetic analogue of spongouridine with improved antiviral activity, originally isolated in 1950 from the sponge Tethya crypta (Sagar et al, 2010), but currently obtained from fermentation cultures of the bacterium Streptomyces antibioticus. Another important marine natural product, ziconotide (commercial name Prialt; Klotz, 2006), is a synthetic calcium-channel binding conotoxin from Conus magus, the Magician's cone snail, which has proved effective in patients with intractable severe pain who either do not respond to or cannot tolerate other drugs.…”

“…To date, the global marine pharmaceutical pipeline consists of seven approved pharmaceuticals in clinical use, four of which are anticancer drugs (Figure 1). The first marinederived anticancer agent to be developed for clinical use, cytarabine or Ara-C, is a synthetic analogue of a C-nucleoside from the Caribbean sponge, Cryptothethya crypta, approved in 1969 and still in use today to treat acute myelocytic leukaemia and non-Hodgkin's lymphoma (Sagar et al, 2010). Almost 20 years later in 2007 the next anticancer agent from the tunicate Ecteinascidia turbinata would be approved, trabectedin (Yondelis), for the treatment of soft tissue sarcomas and ovarian cancer (Schoffski et al, 2008).…”