Blocking viral infections with lysine-based polymeric nanostructures: a critical review.

The outbreak of the Covid-19 pandemic due to the SARS-CoV-2 coronavirus has accelerated the search for innovative antivirals with possibly broad-spectrum efficacy. One of the possible strategies is to inhibit the replication of the virus by preventing or limiting its entry into the cells. Nanomaterials derived from lysine, an essential amino acid capable of forming homopeptides of different shapes and sizes through thermal polymerization, are an exciting antiviral option. In this review, we have critically compared the antiviral activities and mechanisms of action of lysine and its possible analogues in the form of linear, hyperbranched, dendrimer and nanoparticle polymers. The polycationic nature, as well as the structure of polylysine in its various forms, favours the electrostatic interaction with viruses by inhibiting their replication and endocytosis. In the case of lysine alone, the antiviral action is instead carried out inside the cell. The experimental results obtained so far show that the development of antivirals based on amino acids that inhibit the entry of viruses into cells represents a definite possibility for developing challenging solutions against present and future pandemics.

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.