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

**Abdalla E. M. Salih 1, Bathini Thissera 1, Mohammed Yaseen 1, Ahmed S. I. Hassane 1,2, Hesham R. El-Seedi 3,4,5, Ahmed M. Sayed 6,\* and Mostafa E. Rateb 1,\***


**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 agen<sup>t</sup> 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.

**Keywords:** sulfated polysaccharides; antiviral; SARS-CoV-2; docking; molecular dynamic simulations
