Supramolecular Architectures of Dendritic Polymers Provide Irreversible Inhibitor to Block Viral Infection

Area of Science:

• Supramolecular chemistry
• Polymer science
• Virology

Background:

• Biological functions often rely on self-assembled structures like protein complexes and cell membranes.
• Dendritic polymers offer unique properties for biomedical applications.

Purpose of the Study:

• To develop a self-assembled dendritic polymer with potent and irreversible antiviral activity against SARS-CoV-2.
• To investigate the structure-activity relationship of the self-assembled polymer.

Main Methods:

• Synthesis of a dendritic polymer and its monomeric analogs.
• Formation of two-dimensional supramolecular polymers (2D-SupraPol).
• In vitro and in vivo antiviral assays (SARS-CoV-2 inhibition).
• Cryo-transmission electron microscopy (cryo-TEM) and small-angle X-ray/neutron scattering for structural analysis.

Main Results:

• The self-assembled 2D-SupraPol exhibited irreversible inhibition of SARS-CoV-2 with a low IC50 (30 nM).
• Monomeric analogs showed only reversible inhibition, with the virus regaining infectivity upon dilution.
• The 2D-SupraPol demonstrated good efficacy in a Syrian Hamster model.
• Cryo-TEM revealed controllable lateral size of the 2D-SupraPol, tunable by pH.
• Small-angle X-ray and neutron scattering elucidated the supramolecular assembly architecture.

Conclusions:

• Self-assembly into a 2D-SupraPol is crucial for the irreversible virucidal mechanism of the dendritic polymer against SARS-CoV-2.
• The developed 2D-SupraPol is a promising candidate for a prophylactic nasal spray to prevent viral entry into the respiratory tract.