Abstract
Abstract In Nature, most known objects can perform their functions only when in supramolecular self‐assembled from, e.g. protein complexes and cell membranes. Here, a dendritic polymer is presented that inhibits severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with an irreversible (virucidal) mechanism only when self‐assembled into a Two‐dimmensional supramolecular polymer (2D‐SupraPol). Monomeric analogs of the dendritic polymer can only inhibit SARS‐CoV‐2 reversibly, thus allowing for the virus to regain infectivity after dilution. Upon assembly, 2D‐SupraPol shows a remarkable half‐inhibitory concentration (IC 50 30 nM) in vitro and in vivo in a Syrian Hamster model has a good efficacy. Using cryo‐TEM, it is shown that the 2D‐SupraPol has a controllable lateral size that can be tuned by adjusting the pH and use small angle X‐ray and neutron scattering to unveil the architecture of the supramolecular assembly. This functional 2D‐SupraPol, and its supramolecular architecture are proposed, as a prophylaxis nasal spray to inhibit the virus interaction with the respiratory tract.