Abstract
Only a mere fraction of the huge variety of human pathogenic viruses can be targeted by the currently available spectrum of antiviral drugs. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the urgent need for molecules that can be deployed quickly to treat novel, developing or re-emerging viral infections. Sulfated polysaccharides are found on the surfaces of both the susceptible host cells and the majority of human viruses, and thus can play an important role during viral infection. Such polysaccharides widely occurring in natural sources, specifically those converted into sulfated varieties, have already proved to possess a high level and sometimes also broad-spectrum antiviral activity. This antiviral potency can be determined through multifold molecular pathways, which in many cases have low profiles of cytotoxicity. Consequently, several new polysaccharide-derived drugs are currently being investigated in clinical settings. We reviewed the present status of research on sulfated polysaccharide-based antiviral agents, their structural characteristics, structure–activity relationships, and the potential of clinical application. Furthermore, the molecular mechanisms of sulfated polysaccharides involved in viral infection or in antiviral activity, respectively, are discussed, together with a focus on the emerging methodology contributing to polysaccharide-based drug development.
Highlights
Viruses represent opportunistic, replicative units, tightly integrated into the regulatory machinery of their infected host cells and can be found in the entire sphere of living organisms
Karmakar and co-workers (2009) reported the presence of a fucoidan the core region of which is composed primarily of α-(1,2)- and α-(1,3)-linked Fucp residues with sulfate groups at position 4 and 2 [128]. These complex polysaccharides inhibited a wide variety of viruses including HIV [81,129,130,131], herpes simplex virus (HSV) [76,77,79,80,101,132,133,134,135,136,137,138], Influenza virus (IV) [139,140,141,142,143], avian influenza virus (AIV) [144], human cytomegalovirus (HCMV) [132,134], Newcastle disease virus (NDV) [107,145] bovine viral diarrhoea virus [31,78,146], SARS-CoV-2 [82,147,148,149] and murine norovirus [150]
It has been shown to be effective against a number of viruses including Japanese encephalitis virus (JEV) [192], influenza virus (H1N1) [139], dengue virus (DENV) [100], AIV [144], vesicular stomatitis virus [106], measles virus [105], HSV [45,108,134], NDV [107], Indiana vesiculo virus [106], and human metapneumo virus (HMPV) [193]
Summary
Replicative units, tightly integrated into the regulatory machinery of their infected host cells and can be found in the entire sphere of living organisms. A recently proposed cost-effective single-stage process has the ability to generate a large number of sulfated polysaccharides with different structural features from plant materials, and inducing potential biological activities including antiviral activity in the final product [43]. Along with the alteration of the typical hydroxyl groups into sulfates, a functionality that is rarely found in higher plants, this method changes some of the properties (like the MW, composition, sulfate content and others) of the generated sulfated polysaccharides, and, the chances of producing libraries of such polymers with interesting biomolecular properties can be increased [43,44,45,46,47] From this point of view, we focus on sulfated polysaccharides that show antiviral effects on their own. The synthesis of new molecules possessing diverse structures utilizing this cost-effective one-step will be a useful addition to the arsenal of antivirals These sulfated polysaccharides will help to establish an improved understanding of the structure–activity relationship (SAR).
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