Antiviral Strategies Using Natural Source-Derived Sulfated Polysaccharides in the Light of the COVID-19 Pandemic and Major Human Pathogenic Viruses

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.

Molnupiravir - the First Oral Antiviral for COVID-19: A Literature Review

“…The use of carrageenan in nasal sprays or oral drops as a prophylactic and early-stage treatment against the common cold virus and SARS-CoV-2 is considered a very promising aspect that is currently being evaluated in several clinical trials. The current investigation results can help establish the use of polysaccharides as high-value natural antiviral drugs with low side effects (Ray et al, 2022).…”

Gene Set Enrichment Analysis Reveals That Fucoidan Induces Type I IFN Pathways in BMDC

“…In the midst of a viral pandemic, fucoidan has been rapidly garnering interest for its antiviral activity [ 24 , 26 ]. Here, we analyzed global transcriptomic changes in fucoidan-treated BMDCs to better understand fucoidan’s antiviral properties.…”

“…The antiviral effects of fucoidan have been explored in many different in vitro and in vivo infection models, including that of herpes simplex virus (HSV) [ 7 , 8 , 9 , 10 ], human immunodeficiency virus (HIV) [ 11 , 12 , 13 ], human T-lymphotropic virus type-1 (HTLV-1) [ 14 ], avian influenza virus (AIV) [ 15 ], human cytomegalovirus (HCMV) [ 16 ], Newcastle disease virus (NDV) [ 17 , 18 ], influenza virus [ 19 , 20 , 21 ], and hepatitis B virus [ 22 , 23 ]. In recent reports it has been suggested that fucoidan and other sulfated polysaccharides from seaweed have a prophylactic and therapeutic effect against SARS-CoV-2 infection [ 24 , 25 , 26 , 27 ]. While various mechanisms specific to SARS-CoV-2 have been proposed, including binding of the spike glycoprotein to prevent cell entry [ 24 , 28 ], how fucoidan exerts its effects on such a wide variety of viruses remains unknown.…”

Cyanobacteria and Algae-Derived Bioactive Metabolites as Antiviral Agents: Evidence, Mode of Action, and Scope for Further Expansion; A Comprehensive Review in Light of the SARS-CoV-2 Outbreak

“…Moreover, marine algae are also rich in sulfated polysaccharides that prevent the replication of viruses, and they have been clinically tested, e.g., against HSV-1 [ 63 , 64 ]. Sulfated polysaccharides inhibit antiviral pathways and act as potential replication inhibitors of retroviruses such as HIV-V [ 36 ].…”