**4. Conclusions**

To challenge highly virulent SARS CoV-2 and its emerging mutations, which have cost millions of lives, there is an urgen<sup>t</sup> need to ramp up drug discovery pipelines within a short timeframe. In order to shorten the drug development cycle, screening of existing chemical libraries holds greater potential than starting from scratch. The levels of structural and functional diversity of MSPs have been widely discussed for their antiviral properties; however, the depth of these activities in terms of possible mechanisms against potential drug targets has been poorly studied. A large number of members belong to the class of SPs being overlooked as potential candidates to suppress the virulence of SARS CoV-2.

In the present investigation, we aimed to point out the most probable binding sites on S-protein's RBD and ACE2 using a well-known sulfated polysaccharide (i.e., heparin) as a molecular probe. Interestingly, the binding of heparin to these sites led to dissociation of the RBD–ACE2 complex. These MDS-derived results indicated and validated these proposed binding sites as potential targets for further ligands from the same chemical class. Accordingly, these identified binding sites were used in a series of docking experiments using most of the collected MSPs in this report. A number of MSPs were then found to be potential binders to these sites. Most of the identified hits have been reported to exert antiviral activity against SARS CoV-2; however, some of them have not, meaning they are considered very promising candidates for experimental testing. Overall, the present investigation shed light on the huge potential of MSPs as antiviral chemical entities and provided the scientific community hints about their potential against SARS CoV-2, with some important structural information to be utilized in further experimental research.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/10 .3390/md19080406/s1, Figure S1–S8 indicating details about the reported SMPs in addition to the reported SMPs that were reported in the manuscripts.

**Author Contributions:** Conceptualization, A.M.S., M.E.R.; methodology, A.E.M.S., B.T, A.S.I.H., A.M.S.; software, A.E.M.S., A.M.S.; validation, A.E.M.S., B.T., H.R.E.-S., A.M.S., M.Y., M.E.R.; formal analysis, A.E.M.S., A.M.S.; investigation, A.E.M.S., A.M.S., M.E.R.; data curation, B.T., M.Y., A.S.I.H., H.R.E.-S.., A.M.S., M.E.R.; writing—original draft preparation, A.E.M.S., A.M.S.; writing—review and editing, B.T., M.Y., H.R.E.-S., M.E.R.; supervision, M.E.R. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.
