In Vitro Antiviral Activity of Hyperbranched Poly-L-lysine Modified by L-Arginine against Different SARS-CoV-2 Variants

The emergence of SARS-CoV-2 variants requires close monitoring to prevent the reoccurrence
of a new pandemic in the near future. The Omicron variant, in particular, is one of the
fastest-spreading viruses, showing a high ability to infect people and evade neutralization by antibodies
elicited upon infection or vaccination. Therefore, the search for broad-spectrum antivirals
that can inhibit the infectious capacity of SARS-CoV-2 is still the focus of intense research. In the
present work, hyperbranched poly-L-lysine nanopolymers, which have shown an excellent ability to
block the original strain of SARS-CoV-2 infection, were modified with L-arginine. A thermal reaction
at 240 C catalyzed by boric acid yielded Lys-Arg hyperbranched nanopolymers. The ability of
these nanopolymers to inhibit viral replication were assessed for the original, Delta, and Omicron
strains of SARS-CoV-2 together with their cytotoxicity. A reliable indication of the safety profile
and effectiveness of the various polymeric compositions in inhibiting or suppressing viral infection
was obtained by the evaluation of the therapeutic index in an in vitro prevention model. The hyperbranched
L-arginine-modified nanopolymers exhibited a twelve-fold greater therapeutic index when
tested with the original strain. The nanopolymers could also effectively limit the replication of the Omicron strain in a cell culture.