Antiviral Properties of Algal Polysaccharides: History
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Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor:
Dikshansha Rohilla
,
Akhileshwar Kumar Srivastava
,
Rahul Prasad Singh
,
Priya Yadav
,
Sandeep Kumar Singh
,
Dharmendra Kumar
,
Nikunj Bhardwaj
,
Mahipal Singh Kesawat
,
Kapil Deo Pandey
,
Ajay Kumar

Polysaccharides are a group of either similar or different saccharides that are connected with glycosidic bonds. These polysaccharide molecules inhibit viral replication by interfering in any stage of the viral life cycle, which generally takes place in phases such as the adsorption of the virus by the host cells, penetration into the host cell, uncoating of capsids, assembly and release of viral particles, or via inactivating virions before infection. The life cycle of viruses varies from species to species; thus, the action mechanisms of the algal polysaccharides also varies with the nature of the virus species.

  • algal polysaccharides
  • alginic acid
  • COVID-19
  • SARS-CoV-2
  • antiviral activity

1. Introduction

For the last three years, the world has faced an unexpected pandemic of COVID-19, caused by the novel coronavirus (SARS-CoV-2). The outbreak of this virus affects the lives and survivability of human beings. Although, in the last three years, significant progress has been made by the scientific community in developing vaccines that control the virus spread to a certain extent [1][2]. Although the administration of vaccines enhances the immune response of the body to cope against the infection caused by the ever-changing shape of the mutant RNA virus, the identification of different mutant strains always poses a threat, which necessitates the search for an alternative that can enhance the immune response of the body [2]. In this regard, new experiments have been executed regularly to meet the requirement of a novel, efficient, economic, and nontoxic antiviral candidate.
In last two decades, significant progress has been made with algal metabolites in developing different types of drugs to cure human viral or chronic diseases [3][4][5]. Algae are a diverse group of photosynthetic organisms found in both fresh and marine aquatic systems. The ubiquitous nature and survivability of algae under different harsh conditions, such as hot, cold, and intense light conditions, confirms the presence of some specific metabolites in their cells. These metabolites are a rich source of high-value foods and important pharmaceutical compounds [6]. The beneficial secondary metabolites, such as phycocyanin, polysaccharides, lutein, vitamin B12, vitamin E, vitamin K, polyphenols, polyunsaturated fatty acids, and polysaccharides, are well documented in a previous study [7]. In addition, antimicrobial, anti-inflammatory, anticancer, immunosuppressive, and other pharmacologically significant properties of these secondary metabolites have been investigated [8][9][10].
Algal groups are a rich source of secondary metabolites, which have been synthesized during the different phases of growth stages via various metabolic processes [11][12]. However, the cultivation practices and growth conditions are limiting factors during metabolite production [13][14][15]. Although like other metabolites, algal metabolites also constitute different functional groups, including polyphenols, carotenoids, vitamins, lipids, and polysaccharides, which possess a diverse range of medicinal properties, as documented in the previous study [16][17]. For example, calcium spirulan (Ca-SP), a derivative of Spirulina platensis, is reported to inhibit the replication and penetration into the host cells of different viruses such as herpes simplex virus (HSV) type 1, measles, mumps, influenza A virus, and human immunodeficiency virus HIV-1 [18]. Sharaf et al. [19] evaluated the anti-herpetic activity of Arthrospira fusiformi and found the application of A. fusiformis extract inhibits the multiplication of the herpes virus before and after host infection. Similarly, Silva et al. [20] reported cyanobacterial extract significantly inhibits replication of the influenza virus. In another study, Shih et al. [21] evaluated the potential of allophycocyanin isolated from Spirulina platensis against enterovirus and found it had the potential to delay RNA synthesis in the infected cell. Cyanovirin-N, proteins derived from Nostoc ellipsosporum, showed broad-spectrum activity against HIV [22], hepatitis C [23], and influenza [24]. Lectins, a protein derived from algae, are also considered the largest antiviral chemical class, which generally target glycoproteins of the virus envelope and help to control viruses’ entry into the host cells [25][26]. The most effective antiviral drugs include sulfated polysaccharides, phenolic chemicals, and organic acids [27]. The structural composition of COVID-19 possesses similar structural proteins, and therefore preventive measures can be followed by previous research conducted on algal-derived metabolites [28][29].
In last two decades, several virus outbreaks such as swine influenza, avian influenza, and Ebola have emerged [30][31] and the bioactive chemicals generated from algae have been used as a promising antiviral candidate. Nostoc is the genus within the Nostocales order that produces the most metabolites with antibacterial and antiviral activity. Furthermore, Nostoc sp. can withstand a wide range of environmental circumstances, allowing them to thrive in various environments [32][33]. Different marine microalgal species extracts advocated to have thousands of novel bioactive compounds with therapeutic potential could be exploited to produce therapeutic agents against some common human viral diseases [34][35]. Notwithstanding the Brazilian sea, algal crude extracts have been more effective against HSV-1 than HSV-2 [36]. Furthermore, it is warranted to mention that an aqueous extract of Laurencia obtuse showed significant inhibitory potential against influenza virus replication during an in vitro experiment [37]. Furthermore, Zaid et al. [38] demonstrated inhibition in the multiplication of the Coxsackie B4 virus, hepatitis A virus, HSV-1, and HSV-2 by employing seaweed extracts of Ulva Lactuca and Cystoseira myrica in an in vitro study. Thus, the use of different algal metabolites and products offers a way to combat newly emerged viral diseases [39][40].
In the recent past, in silico approaches have been widely used to screen drugs against various diseases in limited time and with less cost [9]. Computational approaches offer several important tools in each step of drug exploration. Various bioinformatics tools are capable of aiding researchers in the recognition and investigation of new drug compounds. The important parameters of in silico methods include virtual screening, molecular docking studies, molecular dynamics simulations, and the determination of ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties [10]. Hence, the current study based on bioinformatic approaches emphasizes the exploration of the potential antiviral activity of algal polysaccharides alginic acid and carrageenan against SARS-CoV-2 targeting the S-RBD protein.

2. The Potential of Algal Polysaccharides as Antiviral Agents

In the recent past, various polysaccharides, such as carrageenan, alginate, ulvans, and laminarins, have been isolated from both fresh and marine water alga and these polysaccharides have been reported for their potential antiviral properties [41]. These polysaccharides, particularly the sulfated polysaccharides, are conferred with strong polyanionic characteristics and have the ability to block the cationic charge upon the surface of cells in order to prevent virus infection or even adsorption [42]. These sulfated polysaccharides have significant therapeutic potential (Table 1); because they can mimic glycosaminoglycans, sugar-rich molecules that are prevalent in cell membranes [43]. Thus, in this research, algal polysaccharides, carrageenans, and alginates are considered to study their impact on SARS-CoV-2.
Table 1. Some common algal polysaccharides used as antiviral agents and their mechanism of action.
Algal Polysaccharides Source Viral Diseases Mechanism of Actions
Carrageenan Red algae Influenza virus
Human immunodeficiency virus
Herpes simplex virus		 The compound inhibits the binding or entry of the virus to the host cell
Alginate Brown algae Human immunodeficiency virus
Hepatitis B Virus		 Compounds inhibit adhesion of virus to the host cell and also inhibit replication inside the cell
Fucan Brown algae Human immunodeficiency virus
Herpes simplex virus		 By blockage of reverse transcriptase
Agar Red algae Influenza virus By the partial blockage of the adhesion to the endothelial cells
Laminaran Brown algae Human immunodeficiency virus By the blockage of reverse transcriptase
Galactan Red algae Human immunodeficiency virus
Herpes simplex virus		 By inhibiting adhesion of the virus to the host cells and inhibition of replication
Ulvans Green algae Human and avian influenza viruses Inhibit viral reproduction
Carrageenans (CGs) are sulfated linear polysaccharides that alternately contain (1→3)-β-D-galactopyranoses and (1→4)-α-D-galactopyranoses substituted with sulfate esters at the several positions [44]. The position of sulfation determines the active properties of the carrageenans. ICGs have been previously well reported in various algal groups, such as Agardhiella, Eucheuma, Chondrus crispus, Furcellaria, Hypnea, Iridaea, Gigartina, Solieria, and Sarconema, accounting for 30–75% of their dry weight [45][46][47]. The multifunctional qualities of the CGs, such as biocompatibility, the absence of toxic effects, biodegradable nature, and emulsifying, gelling, and stabilizing abilities, make them popular in the food, pharmaceutical and cosmetic industries [48]. The presence of antioxidant, antiviral, anti-cancerous, and excellent drug-transport properties make CGs a suitable or multipurpose agent for the pharmaceutical industry [46].
In previous studies, various authors have reported the pharmaceutical properties of CGs against different viral diseases such as the herpes virus types 1 and 2 [49][50], varicella zoster virus [51], cytomegalovirus [52], HIV [53], human metapneumovirus [54], and influenza virus (IAV) [55]. CG has reportedly been found to be most efficient against enveloped viruses. The antiviral effect of the CG structures help in attaching the virus to its receptor [56][57]. In the latest studies, carrageenans such as ι and λ showed strong inhibitory effects against the SARS-CoV-2 virus [58][59][60]. Similarly, Song et al. [61] reported the ability of sulfated polysaccharides, ι -CG, to prevent the binding and penetration of SARS-CoV-2 into host cells.
Alginates, the salts of alginic acid, are polysaccharides comprising 13-(1→4)-D-mannosyluronic acid (M), o~-(1→4)-L-glucosyluronic acid (G), and alternating (MG) blocks [62]. In previously published reports, extraction of alginic acid from various algal groups such as Laminaria, Mcrocystis, and Ascophyllum was well documented [63][64]. Like the CGs, alginates have some specific characteristics such as absence of toxic effect and biocompatible nature, which also make them popular in medical science [47]. Alginates have been used generally in the pharmaceutical industry for microencapsulation, wound dressing, and drug delivery [65]. Numerous authors have reported the use of alginic acid in the treatment of various human viral diseases. For example, Mastromarino et al. [66] reported the antiviral activity of alginic acid against the Vero cells of the enveloped group IV rubella virus. Similarly, Bandyopadhyay et al. [67] reported the antiviral activity of alginate hydrogels against the HSV type-1. Sinha et al. [68] reported an anti-HSV-1 effect of sulfonated alginate, and found that antiviral activity enhanced with increasing sulfate ester content. In addition, different authors have reported the anti-HIV-1 and anti-HSV-1 properties of alginic acid [69][70]. These studies provide a primary clue to the use of these algal polysaccharides in the treatment and prevention SARS-CoV-2.

This entry is adapted from the peer-reviewed paper 10.3390/stresses3030039

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