A newly published study had described the development of a nanoparticle-based formulation capable of completely inhibiting the SARS-CoV-2 infection and blocking the interaction between viral spike protein and host cell ACE2. Various therapeutic interventions like soluble recombinant ACE2 and anti-SARS-CoV-2 neutralizing antibodies, targeting the spike-ACE2 interaction, have been shown to block the viral entry and prevent infection effectively. For the successful delivery of these therapeutics, nanoparticle-based formulations have shown significant efficacy.
The Nanotraps of different diameters (200, 500, and 1200 nm) were designed with biodegradable polylactic acid polymeric core and liposome shell materials. The polylactic acid core was used to ensure mechanical stability and increase the surface area of the Nanotrap. The liposome shell materials covering the core structure were used to mimic the natural functions of a cell membrane. The Nanotrap surface was functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies. The Nanotrap surface was also decorated with phosphatidylserine ligands to ensure viral clearance through macrophage-mediated phagocytosis.
By incubating ACE2-bound and antibody-bound Nanotraps with SARS-CoV-2 spike pseudotyped lentivirus, the scientists observed that both formulations were highly effective in inhibiting SARS-CoV-2 from infecting ACE2-expressing cells. Interestingly, ACE2-bound nanotraps were found to be more effective than antibody-bound Nanotraps in inhibiting viral infection. To determine the therapeutic potency of Nanotraps, the scientists used ex vivo perfused and ventilated healthy, non-transplantable human donor lungs. By injecting the lungs with SARS-CoV-2 pseudovirus and antibody-bound Nanotraps, they observed that Nanotraps were able to inhibit viral infection in the lung tissues completely. Finally, using Vero E6 cells, they confirmed that antibody-bound Nanotraps not only inhibited the infection with authentic SARS-CoV-2 but also outperformed the SARS-CoV-2-inhibiting efficacy of soluble therapeutic antibodies.
Ref Link: https://doi.org/10.1016/j.celrep.2021.109133