Marine Sulfated Polysaccharides as Promising Antiviral Agents: A Comprehensive Report and Modeling Study Focusing on SARS CoV-2

Abstract

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2′s spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein’s RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.

Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors

“… Step 3 (MDS step): Top-scoring poses resulted from the docking step were subjected to 200 ns MD simulations carried out in duplicates. MDS runs were performed and analyzed by Desmond software [ 14 , 15 , 42 , 43 ]. Step 4 (SMD step): steered molecular dynamics (SMD), was carried out to determine the relative binding affinity of the investigated compounds.…”

“…Our group has reacted immediately with the pandemic, putting every effort to screen our available extracts, fractions, and pure compounds obtained from plants, endophytes, and microorganisms of marine and terrestrial origin for the discovery of antiviral hits against SARS-CoV-2 or its main protease (M pro ) as a potential target [ 13 , 14 , 15 , 16 , 17 , 18 ]. In the current study, we report the discovery of a previously reported indole diketopiperazine alkaloid neoechinulin A ( 1 ), as a promising SARS-CoV-2 M pro inhibitor through bioguided screening.…”

Fractionation of sulfated galactan from the red alga Botryocladia occidentalis separates its anticoagulant and anti-SARS-CoV-2 properties

“…However, heparin and derivatives may present severe side effects or complications such as hemorrhage ( 18 , 19 ), thrombocytopenia ( 20 , 21 ), osteoporosis ( 22 , 23 ), hypersensitivity reactions ( 24 ), and hypoaldosteronism ( 25 ). Hence, reports showing potential non-heparin anti-SARS-CoV-2 sulfated glycans, including unique molecules from marine sources, have recently appeared in the literature ( 26 , 27 , 28 , 29 , 30 ). However, these recent reports have studied the actions of the sulfated polysaccharides only against the Wuhan SARS-CoV-2 strain (wild type) and not the mutated variants, including those of more infectious potency.…”

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

“…This is also true for chemically sulfated arabinoxylans, whose antiviral activities vary greatly depending on the degree of sulfation, with highly sulfated polysaccharides being more active [29,46,275]. Incidentally, a modeling study demonstrated that sulfated polysaccharides with a single sulfate or carboxylate group per monosaccharide unit failed to achieve stable binding with either S-protein receptor-binding domain (S-RBD) or ACE2, the human angiotensin-converting enzyme-2 [307] supporting the significance of the extent of sulfation on antiviral efficacy. Moreover, the removal of the sulfate functionality from ulvans [45], fucoidans [73], and chemically sulfated alginates [74,77], glucans [47,275], arabinoxylans [46], and arabinogalactans [44], drastically reduced antiviral activity confirming the importance of sulfate functionality.…”