**1.4.1.1 Low molecular weight compounds with antiviral activity**

Several triterpenes from *G. lucidum* (ganoderiol F, ganodermanontriol and ganoderic acid and B) are active antiviral agents against HIV-1 virus. *In vitro* antiviral activity of influenza viruses type A and B was noticed in extracts of mycelium of mushroom *Kuehneromyces mutabilis* (Schaeff.: Fr.) (Singer & AH Sm.), while the extract and two isolated phenolic components from the mushroom *Inonotus hispidus* (Bull.; Fr.) P. Karst, as well as ergosterol peroxide, are present in many different fungal species.

#### **1.4.1.2 High molecular weight compounds with antiviral activity**

Water-soluble lignins isolated from *Inonotus obliquus* (Pers.: Fr.) Pilate, inhibit HIV protease with IC 50 value of 2.5 mg/ml. Anti-HIV activity is recorded for the submerged culture media of *L. edodes* and water-soluble lignin isolated from the same fungus. Proteinpolysaccharide complex PSK and PSP from *Coriolus versicolor*, also shows antiviral activity on HIV and cytomegalovirus *in vitro*. Inhibition of HIV-1 reverse transcriptase is caused by velutin, protein from *Flammulina velutipes*, which inactivates ribosomes. MD fractions of mushroom *Grifola frondosa* showed general improvement of condition of the patients (85%) who had various symptoms of HIV and other secondary diseases (Zjawioni, 2004).

#### **1.4.2 Antifungal substances**

Compounds with antibacterial and antifungal activity of mushrooms assists in their survival in their environment. These substances can be very useful in the treatment of human infections, but the official antibiotic therapeutics in the world market can be only found originating from microfungi so far. Opportunistic fungal infections are always a big problem, especially in immunocompromised patients receiving chemotherapy or in cases of transplantation of organs or bone marrow, as well as in HIV infection. During the last ten years, the interest in compounds that show antifungal activity has been increased. Among them the sordarin (tricyclic diterpene glycoside) was for the first time isolated in 1971 (Hauer and Sigg as cited in Inouye et al., 2004), and slightly more potent zofimarin was isolated for the first time in 1987 (Ogita et al. 1987 as cited in Inouye et al., 2004). In addition, suggestive is xylarin (compound SCH57404) isolated from the lignicolous fungus *Xylaria s*p. (Schneider, 1995). Many derivatisations of sordarin antibiotics have been performed in research groups of the GlaxoSmith Kline company by biotransformation with *Streptomyces avermitilis*, what resulted in the synthesis of GM237354 (Herreros et al.*,* 1998), with the MIC of 90% that was 0.015 mg/ml for isolates of *C. albicans* and 0.12 for *C. tropicalis*. Further development of these compounds has led to the azasordarin group in which the sugar component is replaced by Nsubstituted morpholine (Herreros et al., 2001 as cited in Inouye et al., 2004).

terpenoids as well as phenolic compounds as the main active components responsible for the

Presented antiviral activity of fungi is related to their whole, complex extracts, but also to the isolated compounds. Agents isolated from fungi can directly cause the inhibition of viral enzymes, the synthesis of viral nucleic acid, or adsorption and absorption of virus in mammalian cells. The most often small molecules are active in the direct antiviral effect, while the indirect effects are mediated by antiviral activity immunostimulative

Several triterpenes from *G. lucidum* (ganoderiol F, ganodermanontriol and ganoderic acid and B) are active antiviral agents against HIV-1 virus. *In vitro* antiviral activity of influenza viruses type A and B was noticed in extracts of mycelium of mushroom *Kuehneromyces mutabilis* (Schaeff.: Fr.) (Singer & AH Sm.), while the extract and two isolated phenolic components from the mushroom *Inonotus hispidus* (Bull.; Fr.) P. Karst, as well as ergosterol

Water-soluble lignins isolated from *Inonotus obliquus* (Pers.: Fr.) Pilate, inhibit HIV protease with IC 50 value of 2.5 mg/ml. Anti-HIV activity is recorded for the submerged culture media of *L. edodes* and water-soluble lignin isolated from the same fungus. Proteinpolysaccharide complex PSK and PSP from *Coriolus versicolor*, also shows antiviral activity on HIV and cytomegalovirus *in vitro*. Inhibition of HIV-1 reverse transcriptase is caused by velutin, protein from *Flammulina velutipes*, which inactivates ribosomes. MD fractions of mushroom *Grifola frondosa* showed general improvement of condition of the patients (85%)

Compounds with antibacterial and antifungal activity of mushrooms assists in their survival in their environment. These substances can be very useful in the treatment of human infections, but the official antibiotic therapeutics in the world market can be only found originating from microfungi so far. Opportunistic fungal infections are always a big problem, especially in immunocompromised patients receiving chemotherapy or in cases of transplantation of organs or bone marrow, as well as in HIV infection. During the last ten years, the interest in compounds that show antifungal activity has been increased. Among them the sordarin (tricyclic diterpene glycoside) was for the first time isolated in 1971 (Hauer and Sigg as cited in Inouye et al., 2004), and slightly more potent zofimarin was isolated for the first time in 1987 (Ogita et al. 1987 as cited in Inouye et al., 2004). In addition, suggestive is xylarin (compound SCH57404) isolated from the lignicolous fungus *Xylaria s*p. (Schneider, 1995). Many derivatisations of sordarin antibiotics have been performed in research groups of the GlaxoSmith Kline company by biotransformation with *Streptomyces avermitilis*, what resulted in the synthesis of GM237354 (Herreros et al.*,* 1998), with the MIC of 90% that was 0.015 mg/ml for isolates of *C. albicans* and 0.12 for *C. tropicalis*. Further development of these compounds has led to the azasordarin group in which the sugar component is replaced by N-

who had various symptoms of HIV and other secondary diseases (Zjawioni, 2004).

substituted morpholine (Herreros et al., 2001 as cited in Inouye et al., 2004).

obtained activity (Turkoglu et al., 2007; Barros et al., 2007; Elmastas et al., 2007).

polysaccharides and other complex molecules (Zjawioni, 2004). **1.4.1.1 Low molecular weight compounds with antiviral activity** 

peroxide, are present in many different fungal species.

**1.4.1.2 High molecular weight compounds with antiviral activity** 

**1.4.1 Antiviral substances** 

**1.4.2 Antifungal substances** 

Several antifungal metabolites with steroid structure have been also isolated from fungi A25822 A and B from *Geotrichum* (Gordee and Butler, 1975 as cited in Inouye et al., 2004) and from *Wallemia sebi*; Mer-NF8054 A and X from the genus *Aspergillus*. The most famous triterpene, favonol isolated from basidiomycetous *Favolashia* sp. (Anke et al., 1995 as cited in Inouye et al., 2004) is a metabolite that exhibited antifungal activity against Ascomycetes, Basidiomycetes, Zygomycetes and Oomycetes, but did not show antibacterial activity. Researchers of Merck Group have discovered four acidic terpenoids from filamentous fungi: ergokonin A (from *Trichoderma koningii*), ascosteroid (from *Ascotricha amphitricha*) arundifungin (steroid from *Arthrinium arundinis*) and enfumafungin (pentacyclic terpenoid from from mould *Trichoderma koningii*), ascosteroid (from ascomycetous *Ascotricha amphitricha*), arundifungin (steroid from mould *Arthrinium arundinis*) and enfumafungin (pentacyclic terpenoid from *Aureobasidium*), which were found to affect the biosynthesis of β-D-glucan but not the biosynthesis of steroids. Among them the best antifungal activity on *Candida* species and species of *Aspergillus* genera showed enfumafungin.
