**2. Red algae and carrageenans**

Red algae (Division: Rhodophyta) are one of the oldest and largest groups of eukaryotic algae with more than 10000 species described (Figure 1). They are distributed worldwide but grow best in waters of near 15°C. They have the characteristic of all eukaryotes including the nuclei which in some algae are smaller than their plastids. However, their cells lack of flagella so they need the water movement to carry masculine cells to the oocyte. They also have disorganized chloroplasts lacking of external endoplasmic reticulum and containing unstacked thylakoids. Their red colour is due to the presence of the phycoerythrin pigment which reflects red light and absorbs blue/green ones. Since blue light penetrates water to a greater depth than light of longer wavelengths, red algae are able to photosynthesize and live in water of 260 m in deep which receive 0.1% of surface irradiance; this means one thousand times less light than the surface. Those rhodophytes that have small amounts of this pigment might seem green or bluish from the chlorophyll and other pigments present in them.

Over the last 2.45 billion years, algae have been diversifying [13] in order to survive in competitive ecological niches. This adaptation led to evolution of a large and diverse array of biochemical constituents.

**Figure 1.** Rhodophyta branched off very early in the tree of life

life [7,8].

interspecies diversity.

pigments present in them.

of biochemical constituents.

**2. Red algae and carrageenans** 

At the present, it remains controversial the inclusion of viruses in the "tree of life". Several authors assume viruses are non-living organisms and believe their properties are driven solely by thermodynamically spontaneous reactions while others give priority to the fact that phylogenetic tree is based on the genomic content of its components, not the physical manifestations of these genomes. Moreover, the fact that viral genomes carried inside virions encode gene products that allow for adaptation and response to changing intracellular and extracellular conditions favors the inclusion of these agents in the tree of

The oligosaccharides chains (glycans) attached to cell surface and extracellular proteins and lipids are known to mediate many important biological roles [9,10]. However, for many glycans, there are still no evident functions that are of obvious benefit to the organism that synthesizes them. In 1949, Haldane postulated "Now every species of mammal and bird so far investigated has shown quite surprising biochemical diversity by serological tests. The antigens concerned seem to be proteins to which polysaccharides are attached. We do not know their functions in the organism, though some of them seem to be part of the structure of the cell membrane. I wish to suggest that they may play a part in disease resistance, a particular race of bacteria or virus being adapted to individuals of a certain range of biochemical constitutions, while those of other constitutions are relatively resistant" [11]. In [12], suggested that glycan diversification in complex multicellular organisms is driven by evolutionary selection pressures of both endogenous and exogenous origin. They also argued that exogenous selection pressures mediated by viral and microbial pathogens and parasites that recognize glycans have played a more prominent role, favoring intra-and

Red algae (Division: Rhodophyta) are one of the oldest and largest groups of eukaryotic algae with more than 10000 species described (Figure 1). They are distributed worldwide but grow best in waters of near 15°C. They have the characteristic of all eukaryotes including the nuclei which in some algae are smaller than their plastids. However, their cells lack of flagella so they need the water movement to carry masculine cells to the oocyte. They also have disorganized chloroplasts lacking of external endoplasmic reticulum and containing unstacked thylakoids. Their red colour is due to the presence of the phycoerythrin pigment which reflects red light and absorbs blue/green ones. Since blue light penetrates water to a greater depth than light of longer wavelengths, red algae are able to photosynthesize and live in water of 260 m in deep which receive 0.1% of surface irradiance; this means one thousand times less light than the surface. Those rhodophytes that have small amounts of this pigment might seem green or bluish from the chlorophyll and other

Over the last 2.45 billion years, algae have been diversifying [13] in order to survive in competitive ecological niches. This adaptation led to evolution of a large and diverse array Red algae contain large quantities of polysaccharides in the cellular wall, thereof, most are sulfated galactans. These galactans are generally constituted by alternatively repeated units of bonds 1,3-α-galactopyranose and 1,4-β-D-galactopyranose can defer in the level and pattern of sulfation, in the substitution by methoxy and/or pyruvate groups and other sugars such as mannose and xylose. They also defer in the 3,6-anhydrogalactose content and the 1,3 -α-galctopyranose residues configuration.

Among these galactans, the carrageenans (CGNs) may be mentioned, which have similar structures to the pattern observed in the galactosaminoglycans. They comprise a wide group of structures that may be divided in two families: the κ-family, defined by the presence of a sulfated C4 group in the unit β-D, and formed by CGNs-κ/ι and the carrageenans-μ/ν, and the λ-family, characterized by a sulfate-C2 group and constituted by all the varieties of λ structures. The λ- and ι-carrageenan types are more strongly sulfated than the most of the heparan sulfate (HS) derived from tissues [14]. In general, this type of carrageenans exhibits a viral inhibitory potential a little greater than the κcarrageenans.

Polysaccharides are composed of building-blocks that although being not numerous, their almost infinite combination led to an array of polysaccharides with an important structural complexity [15]. The diversity of polysaccharides can be further increased by acetylation, methylation and, more commonly in the case of many marine algal polysaccharides, sulfation [16]. Moreover, many algal polysaccharides are metabolically active, either as a storage molecule which undergo structural changes during their life cycles or as a structural component [17].

The sulfated polysaccharides are highly abundant and accessible compounds that may be isolated from various natural sources. Micro- and macroalgae are under investigation for numerous commercial food, agri- and horticultural, pharmaceutical, cosmetic and bioenergy applications [18-21]. Polysaccharides are also known for their wide and variable physicochemical properties which make them suitable for different applications in the fields of medicine and pharmacology. They have proved to be useful tools due to their immune-modulator and antitumoral activity, their interference in the clotting system and in the inflammatory processes, in dermatology, in dietary programs and moreover by affecting the viral replication. Among the natural sources where they can be found are the cell walls from algae. Depending on the type of algae, those with similar structures to the glycosaminoglycans (GAGs) and wide antiviral activity can be isolated [22] (Table 1). Antiviral activity has been documented for retrovirus: human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2), herpesvirus: herpes simplex virus (HSV) type 1 and 2, human cytomegalovirus (HCMV); pseudorabies virus; flavivirus: dengue virus type 2; smallpox virus: variola virus; hepadnavirus: hepatitis B virus (HBV); orthomyxovirus: influenza A virus (inf A); paramyxovirus: respiratory syncytial virus (RSV) and parainfluenza virus; rhabdovirus: vesicular stomatitis virus (VSV); arenavirus: Junin virus, Tacaribe virus and togavirus: Sindbis virus, Semliki Forest virus and against some naked viruses, such as encephalomyocarditis virus, Hepatitis A virus [23] and papilloma virus (HPV) [24], of both DNA and RNA viral types (Table 1). For most of these viruses the initial bond of the virus to the cells would be mainly mediated by the interaction of virus with a GAG of the cellular surface known as HS [14]. In general, sulfated polysaccharides have a chemical structure very similar to the HS. Thus, they might block viral infection by competing against virion attachment to the cell surface.

GAGs are linear polysaccharides constituted of successive repetition of a disaccharide unit which may be sulfated. GAGs can be divided in two groups; Glucosaminoglycans, like HS and galactosaminoglycans like chondroitin sulfate. The initial incorporation of saccharide units of *N*-acetylglucosamine or *N*-acetylgalactosamine, respectively, gives their names. An important difference between these groups is that Glucosaminoglycans are attached by 1,4 union while galactosaminoglycans are attached by 1,3 and 1,4. GAGs are found mainly in the cell surface and in much of the intracellular matrix of the mesodermic tissue as is shown in Table 2 (connective, cartilage, muscle and bone). Frequently, they are linked to a core protein and one or more covalently attached glycosaminoglycan chains, known it as Proteoglycans.

GAGs are negatively charged molecules that can have a physiological significance like hyaluronic acid, dermatan sulfate, chondroitin sulfate, heparin, HS and keratan sulfate.


component [17].

the cell surface.

Proteoglycans.

methylation and, more commonly in the case of many marine algal polysaccharides, sulfation [16]. Moreover, many algal polysaccharides are metabolically active, either as a storage molecule which undergo structural changes during their life cycles or as a structural

The sulfated polysaccharides are highly abundant and accessible compounds that may be isolated from various natural sources. Micro- and macroalgae are under investigation for numerous commercial food, agri- and horticultural, pharmaceutical, cosmetic and bioenergy applications [18-21]. Polysaccharides are also known for their wide and variable physicochemical properties which make them suitable for different applications in the fields of medicine and pharmacology. They have proved to be useful tools due to their immune-modulator and antitumoral activity, their interference in the clotting system and in the inflammatory processes, in dermatology, in dietary programs and moreover by affecting the viral replication. Among the natural sources where they can be found are the cell walls from algae. Depending on the type of algae, those with similar structures to the glycosaminoglycans (GAGs) and wide antiviral activity can be isolated [22] (Table 1). Antiviral activity has been documented for retrovirus: human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2), herpesvirus: herpes simplex virus (HSV) type 1 and 2, human cytomegalovirus (HCMV); pseudorabies virus; flavivirus: dengue virus type 2; smallpox virus: variola virus; hepadnavirus: hepatitis B virus (HBV); orthomyxovirus: influenza A virus (inf A); paramyxovirus: respiratory syncytial virus (RSV) and parainfluenza virus; rhabdovirus: vesicular stomatitis virus (VSV); arenavirus: Junin virus, Tacaribe virus and togavirus: Sindbis virus, Semliki Forest virus and against some naked viruses, such as encephalomyocarditis virus, Hepatitis A virus [23] and papilloma virus (HPV) [24], of both DNA and RNA viral types (Table 1). For most of these viruses the initial bond of the virus to the cells would be mainly mediated by the interaction of virus with a GAG of the cellular surface known as HS [14]. In general, sulfated polysaccharides have a chemical structure very similar to the HS. Thus, they might block viral infection by competing against virion attachment to

GAGs are linear polysaccharides constituted of successive repetition of a disaccharide unit which may be sulfated. GAGs can be divided in two groups; Glucosaminoglycans, like HS and galactosaminoglycans like chondroitin sulfate. The initial incorporation of saccharide units of *N*-acetylglucosamine or *N*-acetylgalactosamine, respectively, gives their names. An important difference between these groups is that Glucosaminoglycans are attached by 1,4 union while galactosaminoglycans are attached by 1,3 and 1,4. GAGs are found mainly in the cell surface and in much of the intracellular matrix of the mesodermic tissue as is shown in Table 2 (connective, cartilage, muscle and bone). Frequently, they are linked to a core protein and one or more covalently attached glycosaminoglycan chains, known it as

GAGs are negatively charged molecules that can have a physiological significance like hyaluronic acid, dermatan sulfate, chondroitin sulfate, heparin, HS and keratan sulfate.

**Table 1.** Antiviral activity of sulfated polysaccharides extracted from marine algae


**Table 2.** Normal distribution of GAGs in the body.
