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

(1) Background: 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 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 compounds and the lactoferrin protein and between 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 extracts can interact with lactoferrin without altering its structural and dynamical properties. Furthermore, 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 may interfere with the mechanism of infection of SARS-CoV-2, especially in the early stages.