We demonstrate that cholesterol-modified polyethylene glycol has antiviral activity, exerted by anchoring to plasma membranes and sterically inhibiting viruses from entering cells. These polymers distribute sparsely on cell membranes even at binding saturation. However, the polymers have sufficient elastic repulsion energy to repel various kinds of viruses with sizes larger than the mean distances between anchored polymers, including SARS-CoV-2 pseudoparticles. Our strategy can be applied to protect the epithelium from viruses. When these polymers are applied to the epithelium, they localize on the apical surface due to the tight junction barriers, resulting in surface-only coating. Therefore, these polymers can prevent the entry of viruses into cells of the epithelium with minimal disturbance to lateral cell-cell interactions and organizations.
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