Recent pandemics highlight the need for broad-spectrum antivirals as viral resistance limits the effectiveness of target-specific drugs. Amphiphilic photosensitizers damage viral lipid membranes more efficiently than cellular membranes due to the lack of antioxidant systems in viruses. Using molecular dynamics simulations of antiviral perylenylethynyluracil analogues, we found that the hydrophobic/hydrophilic nature of the substituent can drive the singlet-oxygen-producing conjugated core into the sub-interfacial zone of the bilayer, which is enriched with freely diffusing oxygen, enabling future developments in perylene-based antiviral design.