**5. Antifungal compounds**

reports the screening results of marine organisms for antiviral activity, and a diverse range of active constituents have been isolated and characterized from them [80, 103, 104]. For some of these isolated substances important antiviral activities were reported. Perhaps the most important antiviral lead of marine origin reported thus far is the nucleoside ara-A (vidarabine) isolated from the sponge *Cryptotethya crypta*. Ara-A is a semisynthetic compound, based on the arabinosyl nucleosides, that inhibits viral DNA synthesis [105]. Once it was realized that biological systems would recognize the nucleoside base after modifications of the sugar moiety, chemists began to substitute the typical pentoses with acyclic entities or with substituted sugars, leading to the drug azidothymidine (zidovudine). Ara-A, ara-C (1-β-Darabinosyl cytosine, cytarabine), acyclovir, and azidothymidine are in clinical use and are all examples of products of semisynthetic modifications of the arabinosyl nucleosides [106]. Several of these substances have a great potential for drug development. Ara-A has been used for the treatment of herpes virus infections, but it is less efficient and more toxic than acyclovir [107, 108]. However, ara-A is capable of inhibiting a cyclovir-resistant HSV and VZV (varicella-zoster virus) [109]. The most promising antiviral substances from sponges appear to be 4-methylaaptamine, avarol, manzamines, mycalamide A and B. Among these substances, preclinical assessments were started for avarol and manzamine A. In general, antiviral molecules from sponges do not give protection against viruses, but they may result in drugs to treat already infected individuals. In addition, broad-based antiviral agents such as 2-5A and α-glucosidase inhibitors may be useful in cases of sudden outbreaks of (less familiar) viruses such as SARS and Ebola [80].

**Categories Species Active agents Antiviral tests References Alkaloid** *Aaptosa aptos* 4-Methylaaptamine HSV-1 [110]

6-deoxymanzamine X neokauluamine

**Nucleosides** *Mycale* sp. Mycalamide A-B A59 coronavirus, HSV-1 [113]

**Cyclic depsipeptides** *Theonella* sp. Papuamides A-D HIV-1 [114]

**Nucleoside** *Cryptotethya crypta* Ara-A HSV-1, HSV-2, VZV [105]

**Miscellaneous** *Dysidea avara* Callyspongymic acid HIV, hepatitis B virus [119]

Indo-Pacific Manzamine A, 8-hydroxymanzamine A,

*Hamacantha* sp. Coscinamides 60-62,

208 Biological Resources of Water

**Sterols** Haplosclerid sponges Haplosamates A HV-1

avarone

**Terpenoids** *D. avara* Avarol 6′-hydroxy avarol, 3′-hydroxy

**Table 3.** Antiviral compounds from marine sponges and their effects.

*Halicortex* sp. Dragmacidin F HSV-1 [111]

*S. microspinosa* Microspinosamide HIV-1 [115]

*Mycale* sp. Mycalamide A-B A59 coronavirus, HSV-1 [118]

*H. tarangaensis* Hamigeran B Herpes, polio viruses [121] *Petrosia weinbergi* Weinbersterols A-B Leukemia virus, mouse influenza

Chondriamides 63-65 Anti-HIV [91]

Haplosamates B [116]

2′-5′ Oligoadenylates Viral replication [120]

HIV-1 [112]

HV-1 [117]

[122]

virus, mouse corona virus

Marine sponges have been considered a gold mine for the discovery of marine natural products during the past 50 years. The need of new antifungals in clinical medicine due to various kinds of mycoses, in particular invasive mycoses have become serious health problems as their incidences has increased dramatically during last few years in relation to AIDS, transplant recipients, hematological malignancies, transplant recipients and other immunosuppressed individuals. One of the major causes of death in patients suffering from malignant disease is fungal infections and emerging resistance is also an important problem. Immunocompromised patients are mainly infected by *Aspergillus*, *Cryptococcus*, *Candida*, and other opportunistic fungi. *Candida albicans* is most often associated with serious invasive fungal infections, but other *Candida* species and yeastlike organisms (*Blastoschizomyces*, *Trichosporon* and *Malassezia*) have emerged as etiological agents of severe mycoses problem [123–126]. Fungicides which are presently being used are less diverse than antimicrobials, and the usage of many of them is restricted because of their toxic effects to animals, plants and humans. Moreover the progress in this area is slow as comparison to antibacterial agents [126]. Antifungal compounds isolated from marine sponges are listed in **Table 4**.



**Table 4.** Antifungal compounds from marine sponges and their effects.
