Interaction of Pelargonium sidoides Compounds with Lactoferrin and SARS-CoV-2: Insights from Molecular Simulations.

(1) Background: Pelargonium sidoides extracts and lactoferrin are two important natural, anti-inflammatory, and antiviral agents, which can interfere with the early stages of SARS-CoV-2 infection. Molecular docking and molecular dynamics simulation approaches have been applied to check for the occurrence of interactions of the Pelargonium sidoides compounds with lactoferrin and with SARS-CoV-2 components. (2) Methods: Computational methods have been applied to confirm the hypothesis of a direct interaction between PEL compounds and the lactoferrin protein and between Pelargonium sidoides compounds and SARS-CoV-2 Spike, 3CLPro, RdRp proteins, and membrane. Selected high-score complexes were structurally investigated through classical molecular dynamics simulation, while the interaction energies were evaluated using the molecular mechanics energies combined with generalized Born and surface area continuum solvation method. (3) Results: Computational analyses suggested that Pelargonium sidoides extracts can interact with lactoferrin without altering its structural and dynamical properties. Furthermore, Pelargonium sidoides compounds should have the ability to interfere with the Spike glycoprotein, the 3CLPro, and the lipid membrane, probably affecting the functional properties of the proteins inserted in the double layer. (4) Conclusion: Our findings suggest that Pelargonium sidoides may interfere with the mechanism of infection of SARS-CoV-2, especially in the early stages.

The Procoagulant Activity of Emoxilane®: A New Appealing Therapeutic Use in Epistaxis of the Combination of Sodium Hyaluronate, Silver Salt, α-tocopherol and D-panthenol.

Epistaxis is one of the most frequent hemorrhages resulting from local or systemic factors. Its management without hospitalization has prompted an interest in locally applied hemostatic agents. Generally, the therapy approaches involve sprays or creams acting as a physical barrier, even used as tampons or gauze. In this study, we have investigated the activity of Emoxilane®, a combination of sodium hyaluronate, silver salt, α-tocopherol acetate and D-panthenol, which is known to be able to separately act in a different biological manner. Our in vitro results, obtained on endothelial and nasal epithelial cells, have shown that the association of these molecules presented a notable antioxidant activity mainly due to the α-tocopherol and D-panthenol and a significant antimicrobial role thanks to the silver compound. Moreover, remarkable hemostatic activity was found by evaluating plasmin inhibition attributable to the sodium hyaluronate. Interestingly, on human plasma, we have confirmed that Emoxilane® strongly induced the increase of thrombin levels. These data suggest that the use of this association could represent an appealing pharmacological approach to actively induce hemostasis during epistaxis. Our future perspective will aim to the creation of a formulation for an easy topical application in the nose which is able to contrast the bleeding.

Antioxidant and antimicrobial properties of Pelargonium sidoides DC and lactoferrin combination.

Lactoferrin (LAT), a multifunctional protein involved in numerous physiological functions, and the medicinal plant Pelargonium sidoides DC (PEL) have been described for their anti-inflammatory properties. Because the main advantage of natural products consists in administering them in combination rather than as single compound, we aimed to understand whether the combination of PEL and LAT, herein PELIRGOSTIM, could still prove beneficial or additive/synergistic activities during inflammatory conditions. To pursue this goal, we used macrophagic cells (J774.1) and treated them with PEL and LAT in a concentration-dependent manner. We found that PELIRGOSTIM was able to reduce the levels of reactive oxygen species (ROS) and nitrite, effects that were correlated to the release of lower levels of IL-1ß after LPS treatment. In addition, the combination of PEL and LAT showed bacteriostatic activities against Staphylococcus aureus and Escherichia coli which had limited growth starting from 5 hours up to 20 hours. This effect was stronger than that observed for penicillin/streptomycin. Our results provide PELIRGOSTIM as an innovative combination of natural products capable to prevent inflammation-, oxidative stress- and microbial-related disorders.