Fucanomics and Galactanomics: Marine Distribution, Medicinal Impact, Conceptions, and Challenges

Glycomics turned out to be a very extensive project where its subdivision is consequently emerging. This is seen by the growing number of terminologies used to define subprojects concerning particular classes of bioactive carbohydrates. Sulfated fucans (SFs) and sulfated galactans (SGs) are relatively new classes of sulfated polysaccharides (SPs) that occur mostly in marine organisms, and exhibit a broad range of medicinal effects. Their structures are taxonomically dependent, and their therapeutic actions include benefits in inflammation, coagulation, thrombosis, angiogenesis, cancer, oxidation, and infections. Some red algae, marine angiosperm and invertebrates express SPs of unique structures composed of regular repeating oligomeric units of well-defined sulfation patterns. This fine pattern of structural regularity is quite rare among any naturally occurring long SPs, and enables accurate structure-biofunction correlations. Seeing that, fucanomics and galactanomics may comprise distinguished glycomics subprojects. We hereby discuss the relevance that justifies the international recognition of these subprojects in the current glycomics age associated with the beneficial outcomes that these glycans may offer in drug development

Marine Antithrombotics

Thrombosis remains a prime reason of mortality worldwide. With the available antithrombotic drugs, bleeding remains the major downside of current treatments. This raises a clinical concern for all patients undergoing antithrombotic therapy. Novel antithrombotics from marine sources offer a promising therapeutic alternative to this pathology. However, for any potential new molecule to be introduced as a real alternative to existing drugs, the exhibition of comparable anticoagulant potential with minimal off-target effects must be achieved. The relevance of marine antithrombotics, particularly sulfated polysaccharides, is largely due to their unique mechanisms of action and lack of bleeding. There have been many investigations in the field and, in recent years, results have confirmed the role of potential marine molecules as alternative antithrombotics. Nonetheless, further clinical studies are required. This review covers the core of the data available so far regarding the science of marine molecules with potential medical applications to treat thrombosis. After a general discussion about the major biochemical steps involved in this pathology, we discuss the key structural and biomedical aspects of marine molecules of both low and high molecular weight endowed with antithrombotic/anticoagulant properties

Effective inhibition of SARS-CoV-2 entry by heparin and enoxaparin derivatives

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused a pandemic of historic proportions and continues to spread globally, with enormous consequences to human health. Currently there is no vaccine, effective therapeutic, or prophylactic. As with other betacoronaviruses, attachment and entry of SARS-CoV-2 are mediated by the spike glycoprotein (SGP). In addition to its well-documented interaction with its receptor, human angiotensin-converting enzyme 2 (hACE2), SGP has been found to bind to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we pseudotyped SARS-CoV-2 SGP on a third-generation lentiviral (pLV) vector and tested the impact of various sulfated polysaccharides on transduction efficiency in mammalian cells. The pLV vector pseudotyped SGP efficiently and produced high titers on HEK293T cells. Various sulfated polysaccharides potently neutralized pLV-S pseudotyped virus with clear structure-based differences in antiviral activity and affinity to SGP. Concentration-response curves showed that pLV-S particles were efficiently neutralized by a range of concentrations of unfractionated heparin (UFH), enoxaparin, 6-O-desulfated UFH, and 6-O-desulfated enoxaparin with 50% inhibitory concentrations (IC50s) of 5.99mg/liter, 1.08mg/liter, 1.77mg/liter, and 5.86mg/liter, respectively. In summary, several sulfated polysaccharides show potent anti-SARS-CoV-2 activity and can be developed for prophylactic as well as therapeutic purposes. IMPORTANCE The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, in late 2019 and its subsequent spread to the rest of the world has created a pandemic situation unprecedented in modern history. While ACE2 has been identified as the viral receptor, cellular polysaccharides have also been implicated in virus entry. The SARS-CoV-2 spike glycoprotein (SGP) binds to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we report structure-based differences in antiviral activity and affinity to SGP for several sulfated polysaccharides, including both well-characterized FDA-approved drugs and novel marine sulfated polysaccharides, which can be developed for prophylactic as well as therapeutic purposes

Study of Marine Natural Products as Anti-SARS-CoV-2 Agents Using Molecular Modeling

Corresponding author (BioMolecular Sciences): Priyanka Samanta, [email protected]://egrove.olemiss.edu/pharm_annual_posters_2022/1018/thumbnail.jp