Effective SARS-CoV-2 antiviral activity of hyperbranched polylysine nanopolymers

The coronavirus pandemic (COVID-19) had spread rapidly since December 2019, when it was first identified in Wuhan, China. As of April 2021, more than 130 million cases have been confirmed, with more than 3 million deaths, making it one of the deadliest pandemics in history. Different approaches must be put in place to confront a new pandemic: community-based behaviours (i.e., isolation and social distancing), antiviral treatments, and vaccines. Although behaviour-based actions have produced significant benefits and several efficacious vaccines are now available, there is still an urgent need for treatment options. Remdesivir represents the first antiviral drug approved by the Food and Drug Administration for COVID-19 but has several limitations in terms of safety and treatment benefits. There is still a strong request for other effective, safe, and broad-spectrum antiviral systems in light of future emergent coronaviruses. Here, we describe a polymeric nanomaterial derived from l-lysine, with an antiviral activity against SARS-CoV-2 associated with a good safety profile in vitro. Nanoparticles of hyperbranched polylysine, synthesized by l-lysine's thermal polymerization catalyzed by boric acid, effectively inhibit the SARS-CoV-2 replication. The virucidal activity is associated with the charge and dimension of the nanomaterial, favouring the electrostatic interaction with the viral surface being only slightly larger than the virions' dimensions. Low-cost production and easiness of synthesis strongly support the further development of such innovative nanomaterials as a tool for potential treatments of COVID-19 and, in general, as broad-spectrum antivirals. This journal i

Tuning Curvature and Stability of Monoolein Bilayers by Designer Lipid-Like Peptide Surfactants

This study reports the effect of loading four different charged designer lipid-like short anionic and cationic peptide surfactants on the fully hydrated monoolein (MO)-based Pn3m phase (Q224). The studied peptide surfactants comprise seven amino acid residues, namely A6D, DA6, A6K, and KA6. D (aspartic acid) bears two negative charges, K (lysine) bears one positive charge, and A (alanine) constitutes the hydrophobic tail. To elucidate the impact of these peptide surfactants, the ternary MO/peptide/water system has been investigated using small-angle X-ray scattering (SAXS), within a certain range of peptide concentrations (R≤0.2) and temperatures (25 to 70°C). We demonstrate that the bilayer curvature and the stability are modulated by: i) the peptide/lipid molar ratio, ii) the peptide molecular structure (the degree of hydrophobicity, the type of the hydrophilic amino acid, and the headgroup location), and iii) the temperature. The anionic peptide surfactants, A6D and DA6, exhibit the strongest surface activity. At low peptide concentrations (R = 0.01), the Pn3m structure is still preserved, but its lattice increases due to the strong electrostatic repulsion between the negatively charged peptide molecules, which are incorporated into the interface. This means that the anionic peptides have the effect of enlarging the water channels and thus they serve to enhance the accommodation of positively charged water-soluble active molecules in the Pn3m phase. At higher peptide concentration (R = 0.10), the lipid bilayers are destabilized and the structural transition from the Pn3m to the inverted hexagonal phase (H2) is induced. For the cationic peptides, our study illustrates how even minor modifications, such as changing the location of the headgroup (A6K vs. KA6), affects significantly the peptide's effectiveness. Only KA6 displays a propensity to promote the formation of H2, which suggests that KA6 molecules have a higher degree of incorporation in the interface than those of A6K

On microstructural transitions of lamellar phase forming surfactants

In binary or ternary surfactant systems, if a complete segregation at an interface between the hydrophilic and lipophilic domains is assumed, the microstructure is related to the interfacial geometry. This is determined by two factors: the local interfacial curvatures set by the balance of molecular forces at the interface, and the interfacial topology and degree of connectivity that is imposed by the need to satisfy global packing constraints. The local constraint is characterized by the packing parameter of the surfactant, upsilon/al. For lipids and membrane mimetic systems this is close to unity. Several microemulsions and liquid-crystalline phases formed from surfactants with surfactant parameter close to unity are shown to exhibit peculiar structural transitions. This is demonstrated by NMR and conductivity experiments. This feature, upsilon/al = 1, shared by lipids, seems to allow quite diverse flexibility in microstructure. This is despite the very different molecular structures of the surfactants studied (DDAB, AOT, MO, PFPE). Microemulsions and liquid-crystalline phases exhibit drastic structural changes on addition of a very small amount of a further new component, or with minimal variation in the composition of the system. Other properties exhibited by such systems are shared and quite general: on increasing the volume fraction of the hydrophobic domain in binary surfactant/water system, or upon water and oil dilution, for microemulsions, an evolution of microstructure from a continuous water network towards closed water domains is observed